2,870 results on '"development"'
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2. A framework for the integration of development and evolution: The forgotten legacy of James Meadows Rendel.
- Author
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Petino Zappala MA
- Subjects
- History, 20th Century, Phylogeny, Genetics, Population history, Biological Evolution, Developmental Biology history
- Abstract
The historical challenges to bridge the gaps between developmental biology and population or statistical genetics under the explanatory dominance of the Modern Evolutionary Synthesis during the 20th century have been thoroughly documented. However, although several attempts to integrate these fields have been made, most have been deemed unsuccessful. As an example of those efforts, in this paper I discuss the work of James Meadows Rendel, a student of J. B. S. Haldane and disciple of Conrad Hal Waddington. I present his largely forgotten or unrecognized, but innovative, ideas about canalization and the role of development in phylogeny as a valuable piece to connect these fields that could still have important ramifications for today's evolutionary biology. In fact, it is expected that the legacy of J. M. Rendel will be rediscovered, and more importantly, incorporated and extended by future researchers, in light of the growth of evolutionary developmental biology in the last decades. What is more, this case offers a chance to critically revisit standard historiographies about the dichotomy between developmental and population genetics research frameworks in 20th century biology., Competing Interests: Declaration of competing interest The author declares that she has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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3. Self-organized collective cell behaviors as design principles for synthetic developmental biology.
- Author
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Hartmann J and Mayor R
- Subjects
- Morphogenesis, Cell Movement, Synthetic Biology, Developmental Biology
- Abstract
Over the past two decades, molecular cell biology has graduated from a mostly analytic science to one with substantial synthetic capability. This success is built on a deep understanding of the structure and function of biomolecules and molecular mechanisms. For synthetic biology to achieve similar success at the scale of tissues and organs, an equally deep understanding of the principles of development is required. Here, we review some of the central concepts and recent progress in tissue patterning, morphogenesis and collective cell migration and discuss their value for synthetic developmental biology, emphasizing in particular the power of (guided) self-organization and the role of theoretical advances in making developmental insights applicable in synthesis., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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4. A special issue of Essays in Biochemistry on evolutionary developmental biology.
- Author
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McGregor AP, Buffry AD, and Vroomans RMA
- Subjects
- Developmental Biology
- Abstract
Evolutionary developmental biology (or evo devo) is a broad field that aims to understand how developmental processes evolve and how this underpins phenotypic change and organismal diversification. This encompasses a need to understand theoretical concepts in evolutionary biology and how tissues, cells, genes, proteins and regulatory elements function and evolve. The articles in this special issue review key topics in the field of evo devo including advances in theory and methodology as well as our latest knowledge about molecular, cellular and organismal functionality and diversification., (© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
- Published
- 2022
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5. The Hazards of Regeneration: From Morgan's Legacy to Evo-Devo.
- Author
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Sinigaglia C, Alié A, and Tiozzo S
- Subjects
- Animals, Biological Evolution, Developmental Biology
- Abstract
In his prominent book Regeneration (1901), T.H. Morgan's collected and synthesized theoretical and experimental findings from a diverse array of regenerating animals and plants. Through his endeavor, he introduced a new way to study regeneration and its evolution, setting a conceptual framework that still guides today's research and that embraces the contemporary evolutionary and developmental approaches.In the first part of the chapter, we summarize Morgan's major tenets and use it as a narrative thread to advocate interpreting regenerative biology through the theoretical tools provided by evolution and developmental biology, but also to highlight potential caveats resulting from the rapid proliferation of comparative studies and from the expansion of experimental laboratory models. In the second part, we review some experimental evo-devo approaches, highlighting their power and some of their interpretative dangers. Finally, in order to further understand the evolution of regenerative abilities, we portray an adaptive perspective on the evolution of regeneration and suggest a framework for investigating the adaptive nature of regeneration., (© 2022. The Author(s).)
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- 2022
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6. Dynamical systems approach to evolution-development congruence: Revisiting Haeckel's recapitulation theory.
- Author
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Kohsokabe T and Kaneko K
- Subjects
- Animals, Feedback, Gene Regulatory Networks, Phylogeny, Biological Evolution, Developmental Biology
- Abstract
It is acknowledged that embryonic development has a tendency to proceed from common toward specific. Ernst Haeckel raised the question of why that tendency prevailed through evolution, and the question remains unsolved. Here, we revisit Haeckel's recapitulation theory, that is, the parallelism between evolution and development through numerical evolution and dynamical systems theory. By using intracellular gene expression dynamics with cell-to-cell interaction over spatially aligned cells to represent the developmental process, gene regulation networks (GRN) that govern these dynamics evolve under the selection pressure to achieve a prescribed spatial gene expression pattern. For most numerical evolutionary experiments, the evolutionary pattern changes over generations, as well as the developmental pattern changes governed by the evolved GRN exhibit remarkable similarity. Changes in both patterns consisted of several epochs where stripes are formed in a short time, whereas for other temporal regimes, the pattern hardly changes. In evolution, these quasi-stationary generations are needed to achieve relevant mutations, whereas, in development, they are due to some gene expressions that vary slowly and control the pattern change. These successive epochal changes in development and evolution are represented as common bifurcations in dynamical systems theory, regulating working network structure from feedforward subnetwork to those containing feedback loops. The congruence is the correspondence between successive acquisitions of subnetworks through evolution and changes in working subnetworks in development. Consistency of the theory with the segmentation gene-expression dynamics is discussed. Novel outlook on recapitulation and heterochrony are provided, testable experimentally by the transcriptome and network analysis., (© 2021 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution Published by Wiley Periodicals LLC.)
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- 2022
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7. Putting the August Krogh principle to work in developmental physiology.
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Burggren WW
- Subjects
- Animals, Developmental Biology, Fishes physiology, Models, Biological
- Abstract
The August Krogh principle has guided many comparative physiological studies, being especially useful for developmental physiology. Several attributes of unusual, if not unique, animals enable researchers to understand developmental phenomena more generally - the essence of the Krogh principle. This article provides examples of unusual traits of animals currently being used to understand development and reproduction. 1) Accelerated development greatly minimizes time spent examining how animals develop across time from egg to adult. For example, the tropical gar begins to breath air within as little as 2.5 days after hatching - much faster than other air-breathing fishes - facilitating study of the development of respiratory reflexes in fishes. 2) Transparency of the body wall has been exploited to image cardiac output in near-microscopic larvae of the zebrafish and mahi mahi, and to capitalize on bacterial biosensors to investigate development of in vivo digestive function in Caenorhabditis elegans. 3) Gigantism, as in the chicken-sized embryos of the emu, or the larvae of the paradoxical frog, allows surgeries not otherwise feasible. 4) Reproductive traits such as polyembryony in armadillos and parthenogenesis in planaria have informed us about classic gene vs. environment questions. Finally, 5) large body mass range enables clearer allometric analyses. Insects like the silk moth, show a more than a 1000-fold difference between eggs and adults. The August Krogh principle, then, is not simply to justify the study of exotic animals (as interesting as that is!), but has been used to generate a broader synthesis and understanding of all taxa., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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8. DNA is not an ontologically distinctive developmental cause.
- Author
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Vecchi D
- Subjects
- Metaphysics, Biological Evolution, Biological Ontologies, DNA, Developmental Biology methods
- Abstract
In this article I critically evaluate the thesis that DNA is an ontologically distinctive developmental cause. I shall critically analyse different versions of the latter thesis by taking into consideration concrete developmental cases. I shall argue that DNA is neither a developmental determinant nor an ontologically distinctive developmental cause. Instead, I shall argue that mechanistic analysis shows that DNA's causal role in development depends on the higher robustness of the developmental processes in which it exerts its causal capacities. The focus on process and developmental system implies a metaphysical shift: rather than attributing to DNA molecules biochemically unique properties, I suggest that it might be better to think about DNA's causal role in development in terms of the causal capacities that DNA molecules manifest in a rich developmental milieu. I shall also suggest that my position is distinct both from the view advocating the instrumental primacy of DNA-centric biology and developmental constructionism. It is different from the former because it provides a substantial answer to the question of what makes DNA causally central in developmental processes. Finally, I argue that evolutionary considerations pose an important challenge to developmental constructionism., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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9. Evolution, kidney development, and chronic kidney disease.
- Author
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Chevalier RL
- Subjects
- Animals, Developmental Biology trends, Epigenesis, Genetic genetics, Gene Expression Regulation, Developmental, Humans, Nephrons cytology, Nephrons embryology, Organogenesis genetics, Renal Insufficiency, Chronic embryology, Renal Insufficiency, Chronic pathology, Developmental Biology methods, Evolution, Molecular, Nephrons metabolism, Renal Insufficiency, Chronic genetics
- Abstract
There is a global epidemic of chronic kidney disease (CKD) characterized by a progressive loss of nephrons, ascribed in large part to a rising incidence of hypertension, metabolic syndrome, and type 2 diabetes mellitus. There is a ten-fold variation in nephron number at birth in the general population, and a 50% overall decrease in nephron number in the last decades of life. The vicious cycle of nephron loss stimulating hypertrophy by remaining nephrons and resulting in glomerulosclerosis has been regarded as maladaptive, and only partially responsive to angiotensin inhibition. Advances over the past century in kidney physiology, genetics, and development have elucidated many aspects of nephron formation, structure and function. Parallel advances have been achieved in evolutionary biology, with the emergence of evolutionary medicine, a discipline that promises to provide new insight into the treatment of chronic disease. This review provides a framework for understanding the origins of contemporary developmental nephrology, and recent progress in evolutionary biology. The establishment of evolutionary developmental biology (evo-devo), ecological developmental biology (eco-devo), and developmental origins of health and disease (DOHaD) followed the discovery of the hox gene family, the recognition of the contribution of cumulative environmental stressors to the changing phenotype over the life cycle, and mechanisms of epigenetic regulation. The maturation of evolutionary medicine has contributed to new investigative approaches to cardiovascular disease, cancer, and infectious disease, and promises the same for CKD. By incorporating these principles, developmental nephrology is ideally positioned to answer important questions regarding the fate of nephrons from embryo through senescence., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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10. The impacts of assumptions on theories of tooth development and evolution at the turn of the nineteenth century.
- Author
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MacCord K
- Subjects
- Animals, Biological Evolution, History, 19th Century, Humans, Developmental Biology history, Tooth growth & development, Zoology history
- Abstract
Throughout the last quarter of the nineteenth century, researchers became increasingly interested in explaining the ways in which mammalian teeth, especially molars, and their complex arrangements of cusps arose along both developmental and evolutionary timescales. By the 1890s, two theories garnered special prominence; the tritubercular theory and the concrescence theory. The tritubercular theory was proposed by Edward Drinker Cope in 1883, and later expanded by Henry Fairfield Osborn in 1888, while the concrescence theory was developed by Carl Röse in 1892. Reviews concerning the evolution of mammalian molar teeth tended to paint the two theories as occupying opposing sides, and debates arose between their main proponents; however, their tenets do not seem logically incompatible. Throughout this paper, I argue that the conflict that arose was due not to the content of the theories, but to a diverse array of commitments Cope, Osborn, and Röse held, which turned into background assumptions within the setting of these theories. This history traces the context in which Cope, Osborn, and Röse developed the tritubercular and concrescence theories, and the ways in which the assumptions that these investigators held influenced their perceptions of their theories.
- Published
- 2019
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11. The causes of things.
- Author
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Burke RD
- Subjects
- Animals, Embryo, Nonmammalian, History, 20th Century, History, 21st Century, Sea Urchins genetics, Developmental Biology history, Embryonic Development genetics, Sea Urchins growth & development
- Abstract
Studies using sea urchins have contributed substantially to our understanding of how a fertilized egg is transformed during embryonic development. This brief review provides a personal perspective of the remarkable advances that have occurred over the past 45 years in our understanding of how urchin embryos work., (© 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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12. The State of Cardiovascular Developmental Biology is Strong - Honoring Dr. Roger Markwald and his Seminal Contributions to the Field.
- Author
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Wessels A
- Subjects
- History, 20th Century, History, 21st Century, Humans, United States, Developmental Biology history, Heart anatomy & histology, Heart growth & development
- Abstract
In August 2017, the Cardiovascular Developmental Biology Center (CDBC), together with the "Department of Regenerative Medicine and Cell Biology (RMCB) at the Medical University of South Carolina (MUSC), organized their 13th Annual CDBC Symposium. During this special event, which was organized in collaboration with The Anatomical Record, the unique and important contributions of Dr. Roger Markwald (known to all of us as Roger) to the field of cardiovascular research were celebrated. Fifteen leading investigators in the field presented their ideas and reported results of their studies to an audience that included many familiar faces from Roger's past and present. This group consisted of established investigators from around the world as well as young and upcoming scientists from local institutions. In their presentations, the platform speakers emphasized the significance of Roger's scientific contributions and advice to their professional development and career. In this Special Issue of The Anatomical Record, we assembled a collection of invited papers written by several attendees of the symposium. The issue also contains a number of articles written by colleagues who, for one reason or the other, were not able to attend the meeting, but expressed their desire to contribute to this special "festschrift" of The Anatomical Record in honor and recognition of Roger's amazing career. Anat Rec, 302:14-18, 2019. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2019
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13. Waddington's epigenetics or the pictorial meetings of development and genetics.
- Author
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Nicoglou A
- Subjects
- Animals, Biological Evolution, History, 20th Century, Developmental Biology history, Embryology history, Epigenesis, Genetic, Epigenomics history
- Abstract
In 1956, in his Principles of Embryology, Conrad Hal Waddington explained that the word "epigenetics" should be used to translate and update Wilhelm Roux' German notion of "Entwicklungsmechanik" (1890) to qualify the studies focusing on the mechanisms of development. When Waddington mentioned it in 1956, the notion of epigenetics was not yet popular, as it would become from the 1980s. However, Waddington referred first to the notion in the late 1930s. While his late allusion clearly reveals that Waddington readily associated the notion of epigenetics with the developmental process, in the contemporary uses of the notion this developmental connotation seems to have disappeared. The advent and success of molecular biology have probably contributed to focusing biologists' attention on the "genetic" or the "non-genetic" over the "developmental". In the present paper, I first examine the links that exist, in Waddington's work, between the classical notion of epigenesis in embryology and those of epigenetics that Waddington proposed to connect, and even synthesize, data both from embryology and genetics. Second, I show that Waddington's own view of epigenetics has changed over time and I analyze how these changes appear through his many representations (both schematic or metaphorical images) of the relationships between genetic signals and developmental processes.
- Published
- 2018
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14. [The dorsoventral inversion: An attempt of synthesis].
- Author
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Louryan S and Vanmuylder N
- Subjects
- Animals, Biological Evolution, History, 18th Century, History, 19th Century, Anatomy, Comparative history, Body Patterning, Developmental Biology history, Embryology history, Gastrula embryology
- Abstract
The invertebrates, with known exception of echinoderms, are hyponeurian and protostomian. By contrast, echinoderms, chordates and vertebrate are epineurian and deuterostomian. Convinced of the uniqueness origin of all species, Etienne Geoffroy Saint Hilaire (1772-1844), had postulated a complete inversion of body plan to explain this difference. He had to face up to the hostility of the fixist Georges Cuvier (1763-1832). Much later, famous embryologists such as Maurice Caullery still believed that this idea was erroneous. However, the progress of comparative embryology and of developmental biology gradually contributed to validate this idea. Based upon ancient and recent literature review, and re-examination of arthropods (Acanthoscelides obtectus Say), amphibians (Discoglossus), echinoderms (sea urchin) and mammals (rodents) embryos, we can raise up difference and common points of the gastrulation processes. The dorsoventral gradient is ensured by the couple Dpp (dorsal in arthropods)/SOG/chordin (ventral in arthropods), which appears as "inverted" in epineurians. Blastopore invagination occurs in arthopods in the ventral region, opposite to the vitellus mass (initially diffuse, then predominant on the dorsal side), whereas it occurs at the vegetative side in other hyponeurians and epineurians. It has been accepted that the BMP inhibits oral development in protostomian, whereas it activates it in Chordates. Therefore we assume, as Lowe does, that the oral cavity of deuterostomians might constitute a new structure related to the branchial system. The comparative analysis of the blastopore' orientation, the sperm penetration site, and the polarity axes of various embryos species allows to follow the different modifications and to hypothesize their relative chronology during evolution., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2018
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15. Ediacaran developmental biology.
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Dunn FS, Liu AG, and Donoghue PCJ
- Subjects
- Animals, Fossils, Biological Evolution, Developmental Biology, Eukaryota
- Abstract
Rocks of the Ediacaran System (635-541 Ma) preserve fossil evidence of some of the earliest complex macroscopic organisms, many of which have been interpreted as animals. However, the unusual morphologies of some of these organisms have made it difficult to resolve their biological relationships to modern metazoan groups. Alternative competing phylogenetic interpretations have been proposed for Ediacaran taxa, including algae, fungi, lichens, rhizoid protists, and even an extinct higher-order group (Vendobionta). If a metazoan affinity can be demonstrated for these organisms, as advocated by many researchers, they could prove informative in debates concerning the evolution of the metazoan body axis, the making and breaking of axial symmetries, and the appearance of a metameric body plan. Attempts to decipher members of the enigmatic Ediacaran macrobiota have largely involved study of morphology: comparative analysis of their developmental phases has received little attention. Here we present what is known of ontogeny across the three iconic Ediacaran taxa Charnia masoni, Dickinsonia costata and Pteridinium simplex, together with new ontogenetic data and insights. We use these data and interpretations to re-evaluate the phylogenetic position of the broader Ediacaran morphogroups to which these taxa are considered to belong (rangeomorphs, dickinsoniomorphs and erniettomorphs). We conclude, based on the available evidence, that the affinities of the rangeomorphs and the dickinsoniomorphs lie within Metazoa., (© 2017 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)
- Published
- 2018
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16. Building a developmental toxicity ontology.
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Baker N, Boobis A, Burgoon L, Carney E, Currie R, Fritsche E, Knudsen T, Laffont M, Piersma AH, Poole A, Schneider S, and Daston G
- Subjects
- Animals, Embryonic Development, Humans, Tretinoin metabolism, Developmental Biology, Toxicity Tests
- Abstract
Background: As more information is generated about modes of action for developmental toxicity and more data are generated using high-throughput and high-content technologies, it is becoming necessary to organize that information. This report discussed the need for a systematic representation of knowledge about developmental toxicity (i.e., an ontology) and proposes a method to build one based on knowledge of developmental biology and mode of action/ adverse outcome pathways in developmental toxicity., Methods: This report is the result of a consensus working group developing a plan to create an ontology for developmental toxicity that spans multiple levels of biological organization., Results: This report provide a description of some of the challenges in building a developmental toxicity ontology and outlines a proposed methodology to meet those challenges. As the ontology is built on currently available web-based resources, a review of these resources is provided. Case studies on one of the most well-understood morphogens and developmental toxicants, retinoic acid, are presented as examples of how such an ontology might be developed., Discussion: This report outlines an approach to construct a developmental toxicity ontology. Such an ontology will facilitate computer-based prediction of substances likely to induce human developmental toxicity., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
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17. Embryonic development of the annual killifish Austrofundulus limnaeus: An emerging model for ecological and evolutionary developmental biology research and instruction.
- Author
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Podrabsky JE, Riggs CL, Romney AL, Woll SC, Wagner JT, Culpepper KM, and Cleaver TG
- Subjects
- Animals, Embryo, Nonmammalian, Fundulidae growth & development, Killifishes embryology, Killifishes growth & development, Models, Animal, Developmental Biology methods, Fundulidae embryology, Gene-Environment Interaction
- Abstract
Background: Austrofundulus limnaeus is an annual killifish from the Maracaibo basin of Venezuela. Annual killifishes are unique among vertebrates in their ability to enter into a state of dormancy at up to three distinct developmental stages termed diapause I, II, and III. These embryos are tolerant of a wide variety of environmental stresses and develop relatively slowly compared with nonannual fishes., Results: These traits make them an excellent model for research on interactions between the genome and the environment during development, and an excellent choice for developmental biology laboratories. Furthermore, A. limnaeus is relatively easy to maintain in a laboratory setting and has a high fecundity, making it an excellent candidate as an emerging model for studies of development, and for defining the limits of developmental buffering in vertebrates., Conclusions: This study reports for the first time on the detailed development of A. limnaeus and provides a photographic and illustrated atlas of embryos on the two developmental trajectories possible in this species. Developmental Dynamics 246:779-801, 2017. © 2017 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists., (© 2017 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.)
- Published
- 2017
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18. Perspectives on the history of evo-devo and the contemporary research landscape in the genomics era.
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Tickle C and Urrutia AO
- Subjects
- Animals, Biological Evolution, Developmental Biology, Genomics
- Abstract
A fundamental question in biology is how the extraordinary range of living organisms arose. In this theme issue, we celebrate how evolutionary studies on the origins of morphological diversity have changed over the past 350 years since the first publication of the Philosophical Transactions of The Royal Society Current understanding of this topic is enriched by many disciplines, including anatomy, palaeontology, developmental biology, genetics and genomics. Development is central because it is the means by which genetic information of an organism is translated into morphology. The discovery of the genetic basis of development has revealed how changes in form can be inherited, leading to the emergence of the field known as evolutionary developmental biology (evo-devo). Recent approaches include imaging, quantitative morphometrics and, in particular, genomics, which brings a new dimension. Articles in this issue illustrate the contemporary evo-devo field by considering general principles emerging from genomics and how this and other approaches are applied to specific questions about the evolution of major transitions and innovations in morphology, diversification and modification of structures, intraspecific morphological variation and developmental plasticity. Current approaches enable a much broader range of organisms to be studied, thus building a better appreciation of the origins of morphological diversity.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'., (© 2016 The Author(s).)
- Published
- 2017
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19. Regenerative Medicine: lessons from Mother Nature.
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Naranjo JD, Scarritt ME, Huleihel L, Ravindra A, Torres CM, and Badylak SF
- Subjects
- Animals, Humans, Developmental Biology, Regenerative Medicine, Tissue Engineering methods
- Abstract
Regenerative medicine strategies for the restoration of functional tissue have evolved from the concept of ex vivo creation of engineered tissue toward the broader concept of in vivo induction of functional tissue reconstruction. Multidisciplinary approaches are being investigated to achieve this goal using evolutionarily conserved principles of stem cell biology, developmental biology and immunology, current methods of engineering and medicine. This evolution from ex vivo tissue engineering to the manipulation of fundamental in vivo tenets of development and regeneration has the potential to capitalize upon the incredibly complex and only partially understood ability of cells to adapt, proliferate, self-organize and differentiate into functional tissue.
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- 2016
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20. Defining "Development".
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Pradeu T, Laplane L, Prévot K, Hoquet T, Reynaud V, Fusco G, Minelli A, Orgogozo V, and Vervoort M
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- Animals, Humans, Biological Evolution, Developmental Biology
- Abstract
Is it possible, and in the first place is it even desirable, to define what "development" means and to determine the scope of the field called "developmental biology"? Though these questions appeared crucial for the founders of "developmental biology" in the 1950s, there seems to be no consensus today about the need to address them. Here, in a combined biological, philosophical, and historical approach, we ask whether it is possible and useful to define biological development, and, if such a definition is indeed possible and useful, which definition(s) can be considered as the most satisfactory., (© 2016 Elsevier Inc. All rights reserved.)
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- 2016
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21. Zebrafish as a model for understanding enteric nervous system interactions in the developing intestinal tract.
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Ganz J, Melancon E, and Eisen JS
- Subjects
- Animals, Humans, Intestines embryology, Models, Genetic, Zebrafish genetics, Developmental Biology methods, Enteric Nervous System growth & development, Intestines growth & development, Zebrafish growth & development
- Abstract
The enteric nervous system (ENS) forms intimate connections with many other intestinal cell types, including immune cells and bacterial consortia resident in the intestinal lumen. In this review, we highlight contributions of the zebrafish model to understanding interactions among these cells. Zebrafish is a powerful model for forward genetic screens, several of which have uncovered genes previously unknown to be important for ENS development. More recently, zebrafish has emerged as a model for testing functions of genes identified in human patients or large-scale human susceptibility screens. In several cases, zebrafish studies have revealed mechanisms connecting intestinal symptoms with other, seemingly unrelated disease phenotypes. Importantly, chemical library screens in zebrafish have provided startling new insights into potential effects of common drugs on ENS development. A key feature of the zebrafish model is the ability to rear large numbers of animals germ free or in association with only specific bacterial species. Studies utilizing these approaches have demonstrated the importance of bacterial signals for normal intestinal development. These types of studies also show how luminal bacteria and the immune system can contribute to inflammatory processes that can feedback to influence ENS development. The excellent optical properties of zebrafish embryos and larvae, coupled with the ease of generating genetically marked cells of both the host and its resident bacteria, allow visualization of multiple intestinal cell types in living larvae and should promote a more in-depth understanding of intestinal cell interactions, especially interactions between other intestinal cell types and the ENS., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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22. The embryonic cell lineage of Caenorhabditis elegans: A modern hieroglyph: The best way to acquire knowledge in Developmental Biology is to learn how this knowledge was derived.
- Author
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Sáenz-Narciso B, Gómez-Orte E, Zheleva A, Torres-Pérez R, and Cabello J
- Subjects
- Animals, Bibliometrics, Caenorhabditis elegans cytology, Cell Lineage, Developmental Biology history, History, 20th Century, History, 21st Century, Humans, Developmental Biology education
- Abstract
Nowadays, in the Internet databases era, certain knowledge is being progressively lost. This knowledge, which we feel is essential and should be acquired through education, is the understanding of how the pioneer researchers faced major questions in their field and made their discoveries., (© 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.)
- Published
- 2015
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23. A guide to study Drosophila muscle biology.
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Weitkunat M and Schnorrer F
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- Animals, Drosophila genetics, Embryo, Nonmammalian, Larva genetics, Larva growth & development, Pupa genetics, Pupa growth & development, Developmental Biology methods, Drosophila growth & development, Muscle Development genetics
- Abstract
The development and molecular composition of muscle tissue is evolutionarily conserved. Drosophila is a powerful in vivo model system to investigate muscle morphogenesis and function. Here, we provide a short and comprehensive overview of the important developmental steps to build Drosophila body muscle in embryos, larvae and pupae. We describe key methods, including muscle histology, live imaging and genetics, to study these steps at various developmental stages and include simple behavioural assays to assess muscle function in larvae and adults. We list valuable antibodies and fly strains that can be used for these different methods. This overview should guide the reader to choose the best marker or the appropriate method to obtain high quality muscle morphogenesis data in Drosophila., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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24. Methods to assess Drosophila heart development, function and aging.
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Ocorr K, Vogler G, and Bodmer R
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- Aging pathology, Animals, Drosophila genetics, Drosophila growth & development, Humans, Aging genetics, Developmental Biology methods, Drosophila Proteins biosynthesis, Heart growth & development
- Abstract
In recent years the Drosophila heart has become an established model for many different aspects of human cardiac disease. This model has allowed identification of disease-causing mechanisms underlying congenital heart disease and cardiomyopathies and has permitted the study of underlying genetic, metabolic and age-related contributions to heart function. In this review we discuss methods currently employed in the analysis of the Drosophila heart structure and function, such as optical methods to infer heart function and performance, electrophysiological and mechanical approaches to characterize cardiac tissue properties, and conclude with histological techniques used in the study of heart development and adult structure., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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25. Helpless infants are learning a foundation model.
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Cusack, Rhodri, Ranzato, Marc'Aurelio, and Charvet, Christine J.
- Subjects
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ARTIFICIAL neural networks , *DEVELOPMENTAL biology , *CHILDBIRTH , *ANIMAL species , *MACHINE learning - Abstract
Human infants are helpless for a protracted period after birth. This has been attributed to maternal constraints causing an early birth while the brain is still immature. However, anatomical studies have shown that relative to other species, human newborn brains are not particularly immature. Consistent with this, neuroimaging studies have shown that the structure and function of many cognitive systems is surprisingly mature in humans at birth. Why else might humans have a protracted helpless period? In machine learning, learning good representations of the environment through self-supervised learning in large deep neural networks yields enormously powerful 'foundation models', which allow better generalisation to new problems and have a higher final performance. We propose that in the helpless period, human infants are learning a foundation model that underpins their later cognition. Humans have a protracted postnatal helplessness period, typically attributed to human-specific maternal constraints causing an early birth when the brain is highly immature. By aligning neurodevelopmental events across species, however, it has been found that humans are not born with especially immature brains compared with animal species with a shorter helpless period. Consistent with this, the rapidly growing field of infant neuroimaging has found that brain connectivity and functional activation at birth share many similarities with the mature brain. Inspired by machine learning, where deep neural networks also benefit from a 'helpless period' of pre-training, we propose that human infants are learning a foundation model: a set of fundamental representations that underpin later cognition with high performance and rapid generalisation. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Evolutionary Implications of Self-Assembling Cybernetic Materials with Collective Problem-Solving Intelligence at Multiple Scales.
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Hartl, Benedikt, Risi, Sebastian, and Levin, Michael
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SWARM intelligence , *MULTIPLE intelligences , *CYBERNETICS , *EVOLUTIONARY algorithms , *STOCHASTIC processes , *DEVELOPMENTAL biology , *MORPHOGENESIS - Abstract
In recent years, the scientific community has increasingly recognized the complex multi-scale competency architecture (MCA) of biology, comprising nested layers of active homeostatic agents, each forming the self-orchestrated substrate for the layer above, and, in turn, relying on the structural and functional plasticity of the layer(s) below. The question of how natural selection could give rise to this MCA has been the focus of intense research. Here, we instead investigate the effects of such decision-making competencies of MCA agential components on the process of evolution itself, using in silico neuroevolution experiments of simulated, minimal developmental biology. We specifically model the process of morphogenesis with neural cellular automata (NCAs) and utilize an evolutionary algorithm to optimize the corresponding model parameters with the objective of collectively self-assembling a two-dimensional spatial target pattern (reliable morphogenesis). Furthermore, we systematically vary the accuracy with which the uni-cellular agents of an NCA can regulate their cell states (simulating stochastic processes and noise during development). This allows us to continuously scale the agents' competency levels from a direct encoding scheme (no competency) to an MCA (with perfect reliability in cell decision executions). We demonstrate that an evolutionary process proceeds much more rapidly when evolving the functional parameters of an MCA compared to evolving the target pattern directly. Moreover, the evolved MCAs generalize well toward system parameter changes and even modified objective functions of the evolutionary process. Thus, the adaptive problem-solving competencies of the agential parts in our NCA-based in silico morphogenesis model strongly affect the evolutionary process, suggesting significant functional implications of the near-ubiquitous competency seen in living matter. [ABSTRACT FROM AUTHOR]
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- 2024
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27. When Size Matters: New Insights on How Seed Size Can Contribute to the Early Stages of Plant Development.
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Boccaccini, Alessandra, Cimini, Sara, Kazmi, Hira, Lepri, Andrea, Longo, Chiara, Lorrai, Riccardo, and Vittorioso, Paola
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SEED size ,DEVELOPMENTAL biology ,BIOLOGICAL fitness ,SEED development ,PLANT evolution - Abstract
The seed habit is the most complex and successful method of sexual reproduction in vascular plants. It represents a remarkable moment in the evolution of plants that afterward spread on land. In particular, seed size had a pivotal role in evolutionary success and agronomic traits, especially in the field of crop domestication. Given that crop seeds constitute one of the primary products for consumption, it follows that seed size represents a fundamental determinant of crop yield. This adaptative feature is strictly controlled by genetic traits from both maternal and zygotic tissues, although seed development and growth are also affected by environmental cues. Despite being a highly exploited topic for both basic and applied research, there are still many issues to be elucidated for developmental biology as well as for agronomic science. This review addresses a number of open questions related to cues that influence seed growth and size and how they influence seed germination. Moreover, new insights on the genetic–molecular control of this adaptive trait are presented. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project
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Dekker, Job, Alber, Frank, Aufmkolk, Sarah, Beliveau, Brian J, Bruneau, Benoit G, Belmont, Andrew S, Bintu, Lacramioara, Boettiger, Alistair, Calandrelli, Riccardo, Disteche, Christine M, Gilbert, David M, Gregor, Thomas, Hansen, Anders S, Huang, Bo, Huangfu, Danwei, Kalhor, Reza, Leslie, Christina S, Li, Wenbo, Li, Yun, Ma, Jian, Noble, William S, Park, Peter J, Phillips-Cremins, Jennifer E, Pollard, Katherine S, Rafelski, Susanne M, Ren, Bing, Ruan, Yijun, Shav-Tal, Yaron, Shen, Yin, Shendure, Jay, Shu, Xiaokun, Strambio-De-Castillia, Caterina, Vertii, Anastassiia, Zhang, Huaiying, and Zhong, Sheng
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Biological Sciences ,Genetics ,Human Genome ,Bioengineering ,1.1 Normal biological development and functioning ,Generic health relevance ,Genome ,Cell Nucleus ,Chromatin ,4D nucleome ,cell cycle ,chromosome folding ,development ,disease model ,genomics technologies ,imaging technologies ,modeling ,nuclear organization ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize cis-determinants and trans-modulators of genome organization, (3) test functional consequences of changes in cis- and trans-regulators, and (4) develop predictive models of genome structure and function.
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- 2023
29. Sculpting the microbiome.
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Hanson, Mark A., Westlake, Hannah E., and Schrankel, Catherine S.
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SCULPTURE , *CYTOLOGY , *EVOLUTIONARY developmental biology , *MULTICELLULAR organisms , *ANTIMICROBIAL peptides , *DEVELOPMENTAL biology - Abstract
The article focuses on recent discoveries in host-microbiome interactions, highlighting advancements in understanding host immune responses, microbial colonization dynamics, and the impact of modern genetic tools on studying these interactions. Topics include insights into host immune receptors and effector interactions with specific microbes and the specialization of microbial niches and metabolites affecting host physiology.
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- 2024
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30. Understanding cell fate acquisition in stem-cell-derived pancreatic islets using single-cell multiome-inferred regulomes
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Zhu, Han, Wang, Gaowei, Nguyen-Ngoc, Kim-Vy, Kim, Dongsu, Miller, Michael, Goss, Georgina, Kovsky, Jenna, Harrington, Austin R, Saunders, Diane C, Hopkirk, Alexander L, Melton, Rebecca, Powers, Alvin C, Preissl, Sebastian, Spagnoli, Francesca M, Gaulton, Kyle J, and Sander, Maike
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Biochemistry and Cell Biology ,Biological Sciences ,Pediatric ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Genetics ,Diabetes ,Stem Cell Research - Induced Pluripotent Stem Cell ,Stem Cell Research - Nonembryonic - Human ,Stem Cell Research ,Underpinning research ,1.1 Normal biological development and functioning ,Metabolic and endocrine ,Adult ,Humans ,Islets of Langerhans ,Pancreas ,Cell Differentiation ,Insulin-Secreting Cells ,Pluripotent Stem Cells ,ATAC-seq ,CDX2 ,RNA-seq ,development ,fetal pancreas ,gene regulatory network ,human pluripotent stem cells ,islets ,pancreas ,serotonin ,signals ,single-cell genomics ,transcription factors ,β cell ,Medical and Health Sciences ,Developmental Biology ,Biochemistry and cell biology - Abstract
Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem-cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and pancreas from childhood and adult donors for comparison. We delineate major cell types, define their regulomes, and describe spatiotemporal gene regulatory relationships between transcription factors. CDX2 emerged as a regulator of enterochromaffin-like cells, which we show resemble a transient, previously unrecognized, serotonin-producing pre-β cell population in fetal pancreas, arguing against a proposed non-pancreatic origin. Furthermore, we observe insufficient activation of signal-dependent transcriptional programs during in vitro β cell maturation and identify sex hormones as drivers of β cell proliferation in childhood. Altogether, our analysis provides a comprehensive understanding of cell fate acquisition in stem-cell-derived islets and a framework for manipulating cell identities and maturity.
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- 2023
31. Superficial white matter across development, young adulthood, and aging: volume, thickness, and relationship with cortical features
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Schilling, Kurt G, Archer, Derek, Rheault, Francois, Lyu, Ilwoo, Huo, Yuankai, Cai, Leon Y, Bunge, Silvia A, Weiner, Kevin S, Gore, John C, Anderson, Adam W, and Landman, Bennett A
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Biomedical and Clinical Sciences ,Medical Physiology ,Neurosciences ,Aging ,Brain Disorders ,Dementia ,Acquired Cognitive Impairment ,Adolescent ,Humans ,Young Adult ,Adult ,Child ,Preschool ,Child ,Middle Aged ,Aged ,Aged ,80 and over ,White Matter ,Cross-Sectional Studies ,Brain ,Gray Matter ,Magnetic Resonance Imaging ,Superficial white matter ,U-fibers ,Tractography ,Lifespan ,Development ,Cognitive Sciences ,Developmental Biology ,Neurology & Neurosurgery ,Medical physiology - Abstract
Superficial white matter (SWM) represents a significantly understudied part of the human brain, despite comprising a large portion of brain volume and making up a majority of cortico-cortical white matter connections. Using multiple, high-quality datasets with large sample sizes (N = 2421, age range 5-100) in combination with methodological advances in tractography, we quantified features of SWM volume and thickness across the brain and across development, young adulthood, and aging. We had four primary aims: (1) characterize SWM thickness across brain regions (2) describe associations between SWM volume and age (3) describe associations between SWM thickness and age, and (4) quantify relationships between SWM thickness and cortical features. Our main findings are that (1) SWM thickness varies across the brain, with patterns robust across individuals and across the population at the region-level and vertex-level; (2) SWM volume shows unique volumetric trajectories with age that are distinct from gray matter and other white matter trajectories; (3) SWM thickness shows nonlinear cross-sectional changes across the lifespan that vary across regions; and (4) SWM thickness is associated with features of cortical thickness and curvature. For the first time, we show that SWM volume follows a similar trend as overall white matter volume, peaking at a similar time in adolescence, leveling off throughout adulthood, and decreasing with age thereafter. Notably, the relative fraction of total brain volume of SWM continuously increases with age, and consequently takes up a larger proportion of total white matter volume, unlike the other tissue types that decrease with respect to total brain volume. This study represents the first characterization of SWM features across the large portion of the lifespan and provides the background for characterizing normal aging and insight into the mechanisms associated with SWM development and decline.
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- 2023
32. A knockout‐first model of H3f3a gene targeting leads to developmental lethality
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Bush, Kelly, Cervantes, Vanessa, Yee, Jennifer Q, Klein, Rachel H, and Knoepfler, Paul S
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Biochemistry and Cell Biology ,Biological Sciences ,Pediatric ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Animals ,Female ,Mice ,Pregnancy ,Embryo ,Mammalian ,Fibroblasts ,Gene Targeting ,Histones ,Mice ,Inbred C57BL ,Mice ,Knockout ,Mutation ,development ,H3f3a ,H3f3b ,histone H3.3 ,mouse knockouts ,neurospheres ,Paediatrics and Reproductive Medicine ,Developmental Biology ,Biochemistry and cell biology - Abstract
Histone variant H3.3 is encoded by two genes, H3f3a and H3f3b, which can be expressed differentially depending on tissue type. Previous work in our lab has shown that knockout of H3f3b causes some neonatal lethality and infertility in mice, and chromosomal defects in mouse embryonic fibroblasts (MEFs). Studies of H3f3a and H3f3b null mice by others have produced generally similar phenotypes to what we found in our H3f3b nulls, but the relative impacts of the loss of either H3f3a or H3f3b have varied depending on the approach and genetic background. Here we used a knockout-first approach to target the H3f3a gene for inactivation in C57BL6 mice. Homozygous H3f3a targeting produced a lethal phenotype at or before birth. E13.5 null embryos had some potential morphological differences from WT littermates including smaller size and reduced head size. An E18.5 null embryo was smaller than its control littermates with several potential defects including small head and brain size as well as small lungs, which would be consistent with a late gestation lethal phenotype. Despite a reduction in H3.3 and total H3 protein levels, the only histone H3 post-translational modification in the small panel assessed that was significantly altered was the unique H3.3 mark phospho-Serine31, which was consistently increased in null neurospheres. H3f3a null neurospheres also exhibited consistent gene expression changes including in protocadherins. Overall, our findings are consistent with the model that there are differential, cell-type-specific contributions of H3f3a and H3f3b to H3.3 functions in epigenetic and developmental processes.
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- 2023
33. Ocular Necessities: A Neuroethological Perspective on Vertebrate Visual Development.
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Hunt, Jasper Elan, Pratt, Kara Geo, and Molnár, Zoltán
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- *
DEVELOPMENTAL biology , *EVOLUTIONARY developmental biology , *XENOPUS laevis , *ANIMAL adaptation , *BRACHYDANIO , *VERTEBRATES , *ANIMAL behavior - Abstract
Background: By examining species-specific innate behaviours, neuroethologists have characterized unique neural strategies and specializations from throughout the animal kingdom. Simultaneously, the field of evolutionary developmental biology (informally, "evo-devo") seeks to make inferences about animals' evolutionary histories through careful comparison of developmental processes between species, because evolution is the evolution of development. Yet despite the shared focus on cross-species comparisons, there is surprisingly little crosstalk between these two fields. Insights can be gleaned at the intersection of neuroethology and evo-devo. Every animal develops within an environment, wherein ecological pressures advantage some behaviours and disadvantage others. These pressures are reflected in the neurodevelopmental strategies employed by different animals across taxa. Summary: Vision is a system of particular interest for studying the adaptation of animals to their environments. The visual system enables a wide variety of animals across the vertebrate lineage to interact with their environments, presenting a fantastic opportunity to examine how ecological pressures have shaped animals' behaviours and developmental strategies. Applying a neuroethological lens to the study of visual development, we advance a novel theory that accounts for the evolution of spontaneous retinal waves, an important phenomenon in the development of the visual system, across the vertebrate lineage. Key Messages: We synthesize literature on spontaneous retinal waves from across the vertebrate lineage. We find that ethological considerations explain some cross-species differences in the dynamics of retinal waves. In zebrafish, retinal waves may be more important for the development of the retina itself, rather than the retinofugal projections. We additionally suggest empirical tests to determine whether Xenopus laevis experiences retinal waves. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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34. Editorial: The future of the homology concept under novel evolutionary paradigms.
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Almeida, Thaís Elias, André, Thiago, Yockteng, Roxana, and Arnone, Maria Ina
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HOMOLOGY (Biology) ,COMPARATIVE biology ,HORIZONTAL gene transfer ,MOLECULAR biology ,DEVELOPMENTAL biology - Abstract
This article discusses the concept of homology in evolutionary biology and how it is being challenged by new findings in evolutionary developmental biology and hybridization. The research topic explores different perspectives on the future of the homology concept and its applications in comparative biology. One paper focuses on the discipline of morphology and argues for its importance in understanding organismal form and its evolutionary implications. Another paper discusses the applications of the homology concept in studying the nervous systems of invertebrates. Overall, the papers highlight the need for a dynamic conceptual framework of homology that integrates genetic arrangements and developmental approaches. [Extracted from the article]
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- 2024
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35. Editorial: In celebration of women in developmental epigenetics.
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Mann, Mellissa R. W., Masako Suzuki, and Valsecchi, Claudia I. Keller
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EPIGENETICS ,GENOMIC imprinting ,HEREDITY ,DEVELOPMENTAL biology ,INSULIN-like growth factor receptors ,PRENATAL exposure delayed effects - Abstract
This editorial, published in the journal Frontiers in Cell & Developmental Biology, focuses on the contributions of women in the field of developmental epigenetics. It acknowledges the gender disparity in academia and publishing, with fewer women in senior positions and fewer women credited as authors. The editorial highlights the pioneering work of women scientists in the field and includes reviews and research articles on topics related to genomic imprinting, epigenetic programming, and developmental exposures. It discusses the impact of epigenetic perturbations on prenatal and perinatal development and long-term health outcomes, as well as the effects of prenatal exposure to cadmium and environmental toxicants on epigenetic alterations. The conclusion emphasizes the importance of gender parity in publishing and the need for progress in this area. [Extracted from the article]
- Published
- 2024
- Full Text
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36. Steroidogenic potential of the gonad during sex differentiation in the rice field frog Hoplobatrachus rugulosus (Anura: Dicroglossidae).
- Author
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Traijitt, Thrissawan, Jaroenporn, Sukanya, Nagasawa, Kazue, Osada, Makoto, Kitana, Noppadon, and Kitana, Jirarach
- Subjects
- *
SEX differentiation (Embryology) , *PADDY fields , *DEVELOPMENTAL biology , *GONADS , *FERTILIZATION in vitro , *RICE diseases & pests , *RICE quality - Abstract
Prior studies demonstrated that gonadal differentiation in the rice field frog, Hoplobatrachus rugulosus, was of an undifferentiated type since all individuals had ovaries at complete metamorphosis. However, the steroidogenic potential of the gonad is still unknown. In this study, H. rugulosus were obtained by stimulating fertilization in the laboratory under natural light and temperature conditions. The gonads were collected and their steroidogenic potential was evaluated by determining the expression level of messenger RNA (mRNA) encoding for cytochrome P450 17‐hydroxylase/C17–20 lyase (CYP17) and cytochrome P450 aromatase (CYP19) using quantitative real‐time RT‐PCR and the localization of CYP17 mRNA in tissues by in situ hybridization. The CYP17 mRNA levels in males at 4–11 weeks postmetamorphosis were higher than in female and intersex gonads. This corresponded to their localization in the gonadal tissues, where CYP17 signals were specifically detected in the Leydig cells of the testis at 5–16 weeks postmetamorphosis but was undetectable in all ovary samples. The CYP19 mRNA levels in females at 4–11 weeks postmetamorphosis was higher than in male and intersex gonads, which corresponded with gonadal development, indicating the potential steroidogenic function of the ovary. Based on the present results, the role of CYP17 and CYP19 mRNA in sex differentiation in H. rugulosus may occur after gonadal sex differentiation and the steroidogenic potential of the gonads exhibited a sexual dimorphic pattern. These results provide a crucial basis for further research on the developmental biology in anuran species. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
37. Glutamine-dependent signaling controls pluripotent stem cell fate
- Author
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Lu, Vivian, Roy, Irena J, Torres, Alejandro, Joly, James H, Ahsan, Fasih M, Graham, Nicholas A, and Teitell, Michael A
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Biochemistry and Cell Biology ,Biological Sciences ,Stem Cell Research - Induced Pluripotent Stem Cell ,Stem Cell Research - Embryonic - Human ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Stem Cell Research ,Regenerative Medicine ,Underpinning research ,1.1 Normal biological development and functioning ,Cell Differentiation ,Cell Lineage ,Endoderm ,Germ Layers ,Glutamine ,Humans ,Mesoderm ,Pluripotent Stem Cells ,auxotroph ,cell fate ,development ,glutamine ,nutrient ,pluripotent stem cell ,prototroph ,Medical and Health Sciences ,Developmental Biology ,Biochemistry and cell biology - Abstract
Human pluripotent stem cells (hPSCs) can self-renew indefinitely or can be induced to differentiate. We previously showed that exogenous glutamine (Gln) withdrawal biased hPSC differentiation toward ectoderm and away from mesoderm. We revealed that, although all three germ lineages are capable of de novo Gln synthesis, only ectoderm generates sufficient Gln to sustain cell viability and differentiation, and this finding clarifies lineage fate restrictions under Gln withdrawal. Furthermore, we found that Gln acts as a signaling molecule for ectoderm that supersedes lineage-specifying cytokine induction. In contrast, Gln in mesoderm and endoderm is the preferred precursor of α-ketoglutarate without a direct signaling role. Our work raises a question about whether the nutrient environment functions directly in cell differentiation during development. Interestingly, transcriptome analysis of a gastrulation-stage human embryo shows that unique Gln enzyme-encoding gene expression patterns may also distinguish germ lineages in vivo. Together, our study suggests that intracellular Gln may help coordinate differentiation of the three germ layers.
- Published
- 2022
38. EPIGENETIC CONTROL OF NEURAL CREST DEVELOPMENT AND NEURAL CREST DERIVED TUMORS
- Author
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Casey-Clyde, Timothy
- Subjects
Developmental biology ,Genetics ,Cellular biology ,craniofacial development ,Development ,Epigenetic ,Neural Crest ,polycomb repressive complex 2 ,PRC2 - Abstract
The neural crest is a multipotent transient cell population that migrates, proliferates, and differentiates in vertebrate embryogenesis and gives rises to a cornucopia of tissue derivatives such as craniofacial bone and cartilage, peripheral nerves, and glia. Congenital malformations including cleft palate and craniosynostosis arise from aberrant development of cranial neural crest cells and their derivatives. Neural crest derived tumors of Schwann cell lineages can arise from single genomic hits in the form of NF2 loss. Considering the low genomic burden of many neural crest derived tumors, we hypothesized that epigenetic regulators, which normally specify cell lineages and maintain cell fates in embryonic development, are mis-regulated in adult neural crest derived tissues, contributing to tumorigenesis and differential tumor radiation responses.Here we use mouse genetics and single cell sequencing to investigate how PRC2, a histone methyltransferase broadly involved in gene repression and maintenance of pluripotency in development, is involved in epigenetic control of post- otic neural crest derivates. We identified Eed, a PRC2 core subunit, as a potent regulator of craniofacial development. Eed deletion in post-migratory neural crest cells was perinatal lethal and knockout embryos presented with severe craniofacial abnormalities consistent with impaired differentiation of osteoblast derivatives. Using targeted primary cell culture gene expression analysis and unbiased scRNA-seq, we discovered changes in transcription factors involved in the proliferation and differentiation of neural crest derivatives including loss of Sox transcription factors and increase in Hox genes. Strikingly, we found an expansion of undifferentiated mesenchymal stem cells and decrease in differentiated osteoblast cells, indicating Eed controls proper differentiation of mesenchymal derivatives that comprise craniofacial structures. Taken together, we establish the embryonic, cellular, and molecular consequences of Eed loss in neural crest derived craniofacial tissues.Next, we investigated more broadly how epigenetic regulation contributes to cancer of neural crest derived cells including the tumorigenesis of schwannomas and schwannoma radiation responses. Using bulk and single-cell bioinformatics, functional genomic approaches, and mechanistic validation, we discovered schwannomas comprise 2 molecular subgroups marked by activation of neural crest signaling pathways or enrichment of immune cells in response to radiotherapy. CRISPRi radiation screening in human schwannoma cells identified the lysine demethylases KDM1A and KDM5C as drivers of radioresistance or radiosensitivity, respectively. Lastly, we integrated single-nuclei ATAC, RNA, and CRISPRi perturbation to identify chromatin accessibility motifs that drive schwannoma cell state evolution and radiation responses.
- Published
- 2024
39. Mapping lineage dynamics of progenitors in the human cerebral cortex
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Keefe, Matthew George
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Developmental biology ,Neurosciences ,cortex ,development ,lineage tracing ,progenitors ,radial glia - Abstract
During development of the cerebral cortex, progenitors give rise to diverse cell types in a spatially and temporally defined fashion, but the fate competence of individual progenitors and the lineage relationships between mature cell types has been difficult to ascertain. In this dissertation, I apply a novel prospective lineage tracing tool utilizing synthetic DNA barcodes to label human cortical progenitors and their resulting daughter cells in order to profile their output throughout neurogenesis. First, I show that cortical progenitors are capable to produce inhibitory interneurons, a cell type that had previously been widely believed to derive only from the ventral ganglionic eminences. In an in vitro model as well as in a xenotransplantation model, individual progenitors give rise to both excitatory and inhibitory neurons. Next, I extend this approach to more thoroughly analyze the temporal dynamics of cortical neurogenesis. Lineage tracing across the late second trimester reveals that inhibitory neurogenesis from dorsal progenitors is not a constant feature of cortical development, but arises prominently after midgestation. Furthermore, I show that excitatory neurogenesis proceeds at the ventricular zone throughout development, particularly by a subset of radial glia known as truncated radial glia. These excitatory neurons include neurons of deep layer identity, which are born throughout the second trimester, not just at early timepoints as had been previously believed. Together, these results shed light on previously unappreciated aspects of human cortical neurogenesis and highlight the diverse lineage potential of individual cortical progenitors.
- Published
- 2024
40. Temporal Regulation of Nematode Development from a Biochemical, Circadian Perspective
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Spangler, Rebecca
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Biochemistry ,Developmental biology ,C. elegans ,Circadian ,Development ,Molting ,Oscillator ,Protein - Abstract
Timing mechanisms are utilized by organisms in a variety of biological functions. From circadian rhythms to nematode development, the genetic networks that underly the keeping of time are complex and thoroughly regulated. Circadian rhythms allow organisms to anticipate daily environmental changes and thus confer an adaptive advantage and the genetic network that governs them is well-established. While much is still to be gleaned about the molecular basis of circadian timekeeping, a model of a rewired developmental timer based on conserved circadian clock orthologs C. elegans, is beginning to emerge. In this dissertation, I discuss the conservation of specific factors and provide new insights that highlight the biochemical mechanisms that regulate C. elegans development. C. elegans are a widely studied model organism, yet little is known about the molecular basis for its temporal control of development. Two intricately linked timers, the molting cycle and heterochronic pathway, coordinate cuticle regeneration and growth with stage-specific cellular events. Several circadian orthologs have established roles in regulating these processes. Chapter 2 describes the homology between nuclear hormone receptors (NHRs), retinoic acid-related nuclear receptor (RORα/β/γ) and NHR-23, transcription factors that activate the expression of a core clock component and drives the transcriptional network that governs nematode molting, respectively. We lay the groundwork for a conserved mode of ligand-binding, as well as identify a separate class of small molecules that bind to NHR-23. The interaction between PERIOD (PER) proteins and its cognate kinase, Casein Kinase 1 and ε (CK1), is integral to determining the phase and timing of circadian rhythms. PER is a stoichiometrically limiting factor in the repressive complex that provides the inhibition of circadian transcription. Stable anchoring of CK1 to PER2 mediates phosphorylation of PER that regulates its stability and abundance in the cell. This interaction is also required for CK1-dependent displacement of the core clock transcription factor from DNA. Chapter 3 demonstrates the C. elegans homologs to PER and CK1, LIN-42 and KIN-20, respectively, interact in a similar mode to regulate C. elegans development. We show that two kinase-binding motifs within the CK1-binding domain (CK1BD; CK1BD-A and CK1BD-B) are conserved enough in LIN-42 to mediate binding to CK1 in vitro. We determine that the expression of LIN-42 and KIN-20 temporally and spatially overlaps and that the CK1BD as well as KIN-20 kinase activity are required from proper molting timing. We further show that phosphorylation of LIN-42 by CK1 leads to kinase inhibition, suggesting a conserved mode of product inhibition whereby phosphoserine(s) anchor into conserved anion binding sites along the kinase active site. In chapter 4, we discuss our recent work to identify a novel regulator of the C. elegans molt cycle. Through in vivo techniques, we show that KIN-20 and a previously uncharacterized ankyrin repeat domain-containing protein (ANKRD49), are similarly expressed temporally and spatially, and interact. We show that C. elegans ANKRD49 binds to human CK1 with nanomolar affinity in vitro, and that this interaction influences kinase activity on LIN-42. An AlphaFold binding model of the complex predicts that stable binding is mediated through the ANKRD49 structured C-terminus and a flexible CK1 helix near the active site that is important for substrate recognition and processing. This model also predicts that the interaction is enhanced via binding of the ANKRD49 unstructured N-terminus to the CK1 substrate binding cleft. We show that deletion of the ANKRD49 unstructured N-terminus as well as mutations near and on the flexible CK1 helix that alter circadian period in mammals, reduce the C. elegans ANKRD49/human CK1 affinity >10-fold. Depletion of ANKRD49 in vivo leads to asynchronous and delayed molting similar to kin-20(null) phenotypes. Given the high conservation of CK1 across organisms as well as several proteome-scale studies that also identify a human ANKRD49/CK1 interaction, this work potentially has broader implications for understanding circadian rhythms and temporal regulation in diverse organisms. In summary, throughout this dissertation I have used an interdisciplinary approach of utilizing biochemistry and in vivo C. elegans genetics, to describe the molecular basis for circadian homolog function in C. elegans development. In addition to the findings discussed herein, this work provides a framework elucidating the molecular underpinnings of nematode timing mechanisms as well as an additional insight into evolutionary conservation of timekeeping mechanisms.
- Published
- 2024
41. MLLT3 Isoforms Regulate Hematopoietic Stem Cell Maturation and Fate Decisions
- Author
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Vavilina-Halstead, Anastasia
- Subjects
Cellular biology ,Developmental biology ,development ,expansion ,hematopoiesis ,Hematopoietic stem cells ,maturation ,transcription factor - Abstract
Hematopoietic stem cell (HSC) transplantation can cure life-threatening blood disorders such as leukemias and inherited blood diseases. However, shortage of HLA-matched donors, which disproportionally affects minorities and patients of mixed ethnic backgrounds, limits the number of patients that can be treated. Ex vivo expansion or de novo generation of transplantable human HSCs has not been successful due to poor understanding of the basic biology underpinning key HSC traits - self-renewal, engraftment and multi-lineage differentiation ability (together referred to as “stemness”). Previous studies identified MLLT3 as a key regulator of stemness in human HSCs whose expansion declines in culture and differentiation, and demonstrated that maintaining MLLT3 expression in culture expands transplantable HSCs. The focus of this is the characterization of a truncated isoform of MLLT3 . Analysis of RNA-seq data and epigenetic marks associated with the MLLT3 gene in human HSCs revealed a second TSS linked to a novel MLLT3 isoform (MLLT3-S), which encodes a truncated protein that can interact with known MLLT3 protein partners such as the Superelongation Complex (SEC) and Dot1L, but is unable to bind chromatin. MLLT3-L and MLLT3-S expression has opposing effects on gene expression and expansion of human HSCs in culture, suggesting distinct but complementary roles for the two isoforms. However, both isoforms of MLLT3 are necessary for proper HSC function. The MLLT3-S enhancer is accessible prior to its induction in fetal liver (FL) HSCs during their maturation, and coincides with downregulation of IGFBP2 expression. IGFBP2 is typically downregulated during HSC maturation, but its renewed expression is required for HSC proliferation in culture and MLLT3-L driven HSC expansion. The interplay between long and short isoforms of MLLT3 in human HSCs may provide a mechanism by which mature HSCs balance between expansion and maintenance modes.
- Published
- 2024
42. CUT homeobox genes: transcriptional regulation of neuronal specification and beyond.
- Author
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Leyva-Díaz, Eduardo
- Subjects
GENETIC regulation ,GENETIC transcription regulation ,HOMEOBOX genes ,GENE expression ,DEVELOPMENTAL biology ,GENE families - Abstract
CUT homeobox genes represent a captivating gene class fulfilling critical functions in the development and maintenance of multiple cell types across a wide range of organisms. They belong to the larger group of homeobox genes, which encode transcription factors responsible for regulating gene expression patterns during development. CUT homeobox genes exhibit two distinct and conserved DNA binding domains, a homeodomain accompanied by one or more CUT domains. Numerous studies have shown the involvement of CUT homeobox genes in diverse developmental processes such as body axis formation, organogenesis, tissue patterning and neuronal specification. They govern these processes by exerting control over gene expression through their transcriptional regulatory activities, which they accomplish by a combination of classic and unconventional interactions with the DNA. Intriguingly, apart from their roles as transcriptional regulators, they also serve as accessory factors in DNA repair pathways through protein-protein interactions. They are highly conserved across species, highlighting their fundamental importance in developmental biology. Remarkably, evolutionary analysis has revealed that CUT homeobox genes have experienced an extraordinary degree of rearrangements and diversification compared to other classes of homeobox genes, including the emergence of a novel gene family in vertebrates. Investigating the functions and regulatory networks of CUT homeobox genes provides significant understanding into the molecular mechanisms underlying embryonic development and tissue homeostasis. Furthermore, aberrant expression or mutations in CUT homeobox genes have been associated with various human diseases, highlighting their relevance beyond developmental processes. This review will overview the well known roles of CUT homeobox genes in nervous system development, as well as their functions in other tissues across phylogeny. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
43. Patterns of selection across gene regulatory networks.
- Author
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McDonald, Jeanne M.C. and Reed, Robert D.
- Subjects
- *
BIOLOGICAL evolution , *EVOLUTIONARY developmental biology , *GENE regulatory networks , *PHENOTYPIC plasticity , *DEVELOPMENTAL biology , *NATURAL selection , *GENETIC mutation , *AGRICULTURAL diversification - Abstract
Gene regulatory networks (GRNs) are the core engine of organismal development. If we would like to understand the origin and diversification of phenotypes, it is necessary to consider the structure of GRNs in order to reconstruct the links between genetic mutations and phenotypic change. Much of the progress in evolutionary developmental biology, however, has occurred without a nuanced consideration of the evolution of functional relationships between genes, especially in the context of their broader network interactions. Characterizing and comparing GRNs across traits and species in a more detailed way will allow us to determine how network position influences what genes drive adaptive evolution. In this perspective paper, we consider the architecture of developmental GRNs and how positive selection strength may vary across a GRN. We then propose several testable models for these patterns of selection and experimental approaches to test these models. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. Devo-Aging: Intersections Between Development and Aging.
- Author
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Silva-García, Carlos Giovanni
- Subjects
DEVELOPMENTAL biology ,AGING ,EMBRYOLOGY ,CELLULAR signal transduction ,AGE factors in disease ,CONTINUITY - Abstract
There are two fundamental questions in developmental biology. How does a single fertilized cell give rise to a whole body? and how does this body later produce progeny? Synchronization of these embryonic and postembryonic developments ensures continuity of life from one generation to the next. An enormous amount of work has been done to unravel the molecular mechanisms behind these processes, but more recently, modern developmental biology has been expanded to study development in wider contexts, including regeneration, environment, disease, and even aging. However, we have just started to understand how the mechanisms that govern development also regulate aging. This review discusses examples of signaling pathways involved in development to elucidate how their regulation influences healthspan and lifespan. Therefore, a better knowledge of developmental signaling pathways stresses the possibility of using them as innovative biomarkers and targets for aging and age-related diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
45. Vertebrate cells differentially interpret ciliary and extraciliary cAMP
- Author
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Truong, Melissa E, Bilekova, Sara, Choksi, Semil P, Li, Wan, Bugaj, Lukasz J, Xu, Ke, and Reiter, Jeremy F
- Subjects
1.1 Normal biological development and functioning ,Underpinning research ,Generic health relevance ,Animals ,Cell Line ,Cilia ,Cyclic AMP ,Cyclic AMP-Dependent Protein Kinases ,Cytoplasm ,Hedgehog Proteins ,Neurons ,Optogenetics ,Receptors ,G-Protein-Coupled ,Signal Transduction ,Zebrafish ,G protein-coupled receptor ,Hedgehog signaling ,cAMP ,chemogenetics ,development ,optogenetics ,primary cilia ,protein kinase A ,signal transduction ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Hedgehog pathway components and select G protein-coupled receptors (GPCRs) localize to the primary cilium, an organelle specialized for signal transduction. We investigated whether cells distinguish between ciliary and extraciliary GPCR signaling. To test whether ciliary and extraciliary cyclic AMP (cAMP) convey different information, we engineered optogenetic and chemogenetic tools to control the subcellular site of cAMP generation. Generating equal amounts of ciliary and cytoplasmic cAMP in zebrafish and mammalian cells revealed that ciliary cAMP, but not cytoplasmic cAMP, inhibited Hedgehog signaling. Modeling suggested that the distinct geometries of the cilium and cell body differentially activate local effectors. The search for effectors identified a ciliary pool of protein kinase A (PKA). Blocking the function of ciliary PKA, but not extraciliary PKA, activated Hedgehog signal transduction and reversed the effects of ciliary cAMP. Therefore, cells distinguish ciliary and extraciliary cAMP using functionally and spatially distinct pools of PKA, and different subcellular pools of cAMP convey different information.
- Published
- 2021
46. Gwyneth Ingram.
- Subjects
- *
WOMEN in science , *BOTANY , *DEVELOPMENTAL biology , *PLANT cuticle , *ORNAMENTAL plants - Abstract
This document is an interview with Gwyneth Ingram, a plant scientist, published in the New Phytologist journal. Ingram discusses her interest in plant science, her decision to pursue a career in research, her motivation on a day-to-day basis, and her role models. She also mentions her favorite papers from the journal, which focus on topics such as cuticle architecture, metabolic imaging, and guard cells in fern stomata. Additionally, Ingram shares her favorite plant, the medlar, and provides a brief overview of her educational and professional background. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
47. Dendritic morphology and inhibitory regulation distinguish dentate semilunar granule cells from granule cells through distinct stages of postnatal development
- Author
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Gupta, Akshay, Proddutur, Archana, Chang, Yun-Juan, Raturi, Vidhatri, Guevarra, Jenieve, Shah, Yash, Elgammal, Fatima S, and Santhakumar, Vijayalakshmi
- Subjects
Biomedical and Clinical Sciences ,Medical Physiology ,Neurosciences ,Pediatric ,Animals ,Dendrites ,Dentate Gyrus ,Inhibitory Postsynaptic Potentials ,Male ,Neural Inhibition ,Neurons ,Rats ,Wistar ,Inhibition ,GABA ,Dentate gyrus ,Extrasynaptic ,Development ,Granule cell ,Semilunar granule cell ,Cognitive Sciences ,Developmental Biology ,Neurology & Neurosurgery ,Medical physiology - Abstract
Semilunar granule cells (SGCs) have been proposed as a morpho-functionally distinct class of hippocampal dentate projection neurons contributing to feedback inhibition and memory processing in juvenile rats. However, the structural and physiological features that can reliably classify granule cells (GCs) from SGCs through postnatal development remain unresolved. Focusing on postnatal days 11-13, 28-42, and > 120, corresponding with human infancy, adolescence, and adulthood, we examined the somato-dendritic morphology and inhibitory regulation in SGCs and GCs to determine the cell-type specific features. Unsupervised cluster analysis confirmed that morphological features reliably distinguish SGCs from GCs irrespective of animal age. SGCs maintain higher spontaneous inhibitory postsynaptic current (sIPSC) frequency than GCs from infancy through adulthood. Although sIPSC frequency in SGCs was particularly enhanced during adolescence, sIPSC amplitude and cumulative charge transfer declined from infancy to adulthood and were not different between GCs and SGCs. Extrasynaptic GABA current amplitude peaked in adolescence in both cell types and was significantly greater in SGCs than in GCs only during adolescence. Although GC input resistance was higher than in SGCs during infancy and adolescence, input resistance decreased with developmental age in GCs, while it progressively increased in SGCs. Consequently, GCs' input resistance was significantly lower than SGCs in adults. The data delineate the structural features that can reliably distinguish GCs from SGCs through development. The results reveal developmental differences in passive membrane properties and steady-state inhibition between GCs and SGCs which could confound their use in classifying the cell types.
- Published
- 2020
48. GATA6 mutations in hiPSCs inform mechanisms for maldevelopment of the heart, pancreas, and diaphragm.
- Author
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Sharma, Arun, Wasson, Lauren K, Willcox, Jon Al, Morton, Sarah U, Gorham, Joshua M, DeLaughter, Daniel M, Neyazi, Meraj, Schmid, Manuel, Agarwal, Radhika, Jang, Min Young, Toepfer, Christopher N, Ward, Tarsha, Kim, Yuri, Pereira, Alexandre C, DePalma, Steven R, Tai, Angela, Kim, Seongwon, Conner, David, Bernstein, Daniel, Gelb, Bruce D, Chung, Wendy K, Goldmuntz, Elizabeth, Porter, George, Tristani-Firouzi, Martin, Srivastava, Deepak, Seidman, Jonathan G, Seidman, Christine E, and Pediatric Cardiac Genomics Consortium
- Subjects
Pediatric Cardiac Genomics Consortium ,CRISPR ,development ,developmental biology ,gene mutation ,heart ,human ,iPSC ,regenerative medicine ,stem cells ,Biochemistry and Cell Biology - Abstract
Damaging GATA6 variants cause cardiac outflow tract defects, sometimes with pancreatic and diaphragmic malformations. To define molecular mechanisms for these diverse developmental defects, we studied transcriptional and epigenetic responses to GATA6 loss of function (LoF) and missense variants during cardiomyocyte differentiation of isogenic human induced pluripotent stem cells. We show that GATA6 is a pioneer factor in cardiac development, regulating SMYD1 that activates HAND2, and KDR that with HAND2 orchestrates outflow tract formation. LoF variants perturbed cardiac genes and also endoderm lineage genes that direct PDX1 expression and pancreatic development. Remarkably, an exon 4 GATA6 missense variant, highly associated with extra-cardiac malformations, caused ectopic pioneer activities, profoundly diminishing GATA4, FOXA1/2, and PDX1 expression and increasing normal retinoic acid signaling that promotes diaphragm development. These aberrant epigenetic and transcriptional signatures illuminate the molecular mechanisms for cardiovascular malformations, pancreas and diaphragm dysgenesis that arise in patients with distinct GATA6 variants.
- Published
- 2020
49. Forced to communicate: Integration of mechanical and biochemical signaling in morphogenesis
- Author
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Kindberg, Abigail, Hu, Jimmy K, and Bush, Jeffrey O
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Bioengineering ,Animals ,Biomechanical Phenomena ,Cell Count ,Humans ,Mechanotransduction ,Cellular ,Models ,Biological ,Morphogenesis ,Signal Transduction ,Force ,Signaling ,Actomyosin ,Tension ,Yap ,Taz ,Eph ,Ephrin ,PIEZO ,Development ,Developmental Biology ,Biochemistry and cell biology - Abstract
Morphogenesis is a physical process that requires the generation of mechanical forces to achieve dynamic changes in cell position, tissue shape, and size as well as biochemical signals to coordinate these events. Mechanical forces are also used by the embryo to transmit detailed information across space and detected by target cells, leading to downstream changes in cellular properties and behaviors. Indeed, forces provide signaling information of complementary quality that can both synergize and diversify the functional outputs of biochemical signaling. Here, we discuss recent findings that reveal how mechanical signaling and biochemical signaling are integrated during morphogenesis and the possible context-specific advantages conferred by the interactions between these signaling mechanisms.
- Published
- 2020
50. Human embryoids: A new strategy of recreating the first steps of embryonic development in vitro.
- Author
-
Zhang, Miaoci, Reis, Alice H., and Simunovic, Mijo
- Subjects
- *
EMBRYOLOGY , *DEVELOPMENTAL biology , *HUMAN embryonic stem cells , *HUMAN embryos , *EMBRYONIC stem cells , *HUMAN embryology - Abstract
Molecular mechanisms surrounding early human embryonic events such as blastocyst formation, implantation, and the specification of the body axes are some of the most attractive research questions of developmental biology today. A knowledge on the detailed signaling landscape underlying these critical events in the human could impact the way we treat early pregnancy disorders and infertility, and considerably advance our abilities to make precise human tissues in a lab. However, owing to ethical, technical, and policy restrictions, research on early human embryo development historically stalled behind animal models. The rapid progress in 3D culture of human embryonic stem cells over the past years created an opportunity to overcome this critical challenge. We review recently developed strategies of making 3D models of the human embryo built from embryonic stem cells, which we refer to as embryoids. We focus on models aimed at reconstituting the 3D epithelial characteristics of the early human embryo, namely the intra/extraembryonic signaling crosstalk, tissue polarity, and embryonic cavities. We identify distinct classes of embryoids based on whether they explicitly include extraembryonic tissues and we argue for the merit of compromising on certain aspects of embryo mimicry in balancing the experimental feasibility with ethical considerations. Human embryoids open gates toward a new field of synthetic human embryology, allowing to study the long inaccessible stages of early human development at unprecedented detail. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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