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The signals that regulate peripheral blood vessel formation during development are still under investigation. The hormone leptin promotes blood vessel formation, adipose tissue establishment and expansion, tumor growth, and wound healing, but the underlying mechanisms for these actions are currently unknown. We investigated whether leptin promotes angiogenesis in the developing tail fin using embryonic transgenic xflk-1:GFP Xenopus laevis, which express a green fluorescent protein on vascular endothelial cells to mark blood vessels. We found that leptin protein is expressed in endothelial cells of developing blood vessels and that leptin treatment via injection increased phosphorylated STAT3 signaling, which is indicative of leptin activation of its receptor, in blood vessels of the larval tail fin. Leptin administration via media increased vessel length, branching, and reconnection with the cardinal vein, while decreased leptin signaling via immunoneutralization had an opposing effect on vessel development. We also observed disorganization of major vessels and microvessels of the tail fin and muscle when leptin signaling was decreased. Reduced leptin signaling lowered mRNA expression of cenpk , gpx1 , and mmp9 , markers for cell proliferation, antioxidation, and extracellular matrix remodeling/cell migration, respectively, in the developing tail, providing insight into three possible mechanisms underlying leptin's promotion of angiogenesis. Together these results illustrate that leptin levels are correlated with embryonic angiogenesis and that leptin coordinates multiple aspects of blood vessel growth and development, showing that leptin is an important morphogen during embryonic development. [Display omitted] • Leptin protein localizes and signals in blood vessels of Xenopus embryos. • Leptin increases multiple dimensions of blood vessel growth in the tadpole tail. • Decreased leptin signaling reduces vessel growth and disrupts organization. • Leptin signaling modulates expression of proliferation and ECM remodeling genes. • First evidence linking leptin and peripheral angiogenesis in vertebrate embryos. [ABSTRACT FROM AUTHOR]

• Microglia genetic capacity associates with white matter developmental trajectories. • Microglia genetic capacity is a factor of differential susceptibility. • White matter trajectories mediated microglia associations with social problems. • Findings show sex specificity; only observed in females. There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score (ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes. A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors. Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females. We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems. In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA. Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposures through influences on neurodevelopment. [ABSTRACT FROM AUTHOR]

Dicer substrate interfering RNAs (DsiRNAs) destroy targeted transcripts using the RNA-Induced Silencing Complex (RISC) through a process called RNA interference (RNAi). This process is ubiquitous among eukaryotes. Here we report the utility of DsiRNA in embryos of the sea urchin Lytechinus variegatus (Lv). Specific knockdowns phenocopy known morpholino and inhibitor knockdowns, and DsiRNA offers a useful alternative to morpholinos. Methods are described for the design of specific DsiRNAs that lead to destruction of targeted mRNA. DsiRNAs directed against pks1 , an enzyme necessary for pigment production, show how successful DsiRNA perturbations are monitored by RNA in situ analysis and by qPCR to determine relative destruction of targeted mRNA. DsiRNA-based knockdowns phenocopy morpholino- and drug-based inhibition of nodal and lefty. Other knockdowns demonstrate that the RISC operates early in development as well as on genes that are first transcribed hours after gastrulation is completed. Thus, DsiRNAs effectively mediate destruction of targeted mRNA in the sea urchin embryo. The approach offers significant advantages over other widely used methods in the urchin in terms of cost, and ease of procurement, and offers sizeable experimental advantages in terms of ease of handling, injection, and knockdown validation. • DsiRNA provides an RNAi approach for perturbation of sea urchin embryos. • A dilution series of DsiRNA oligos reveals properties of the Nodal gradient in establishing the Dorsal-Ventral axis. [ABSTRACT FROM AUTHOR]

The lack of a widely accessible method for expressing genes of interest in wild-type embryos is a fundamental obstacle to understanding genetic regulation during embryonic development. In particular, only a few methods are available for introducing gene expression vectors into cells prior to neural tube closure, which is a period of drastic development for many tissues. In this study, we present a simple technique for injecting vectors into the amniotic cavity and allowing them to reach the ectodermal cells and the epithelia of endodermal organs of mouse embryos at E8.0 via in utero injection, using only a widely used optical fiber with an illuminator. Using this technique, retroviruses can be introduced to facilitate the labeling of cells in various tissues, including the brain, spinal cord, epidermis, and digestive and respiratory organs. We also demonstrated in utero electroporation of plasmid DNA into E7.0 and E8.0 embryos. Taking advantage of this method, we reveal the association between Ldb1 and the activity of the Neurog2 transcription factor in the mouse neocortex. This technique can aid in analyzing the roles of genes of interest during endo- and ectodermal development prior to neural tube closure. [Display omitted] • New gene transfection method for embryos at E7 and E8 before neural tube closure. • Only optical fiber and injector needed. • Gene transfection into progenitors in ecto- and endodermal tissues. • Useful to analyze the role of lethal genes during embryogenesis, such as Ldb1. [ABSTRACT FROM AUTHOR]

The ellipsoid body (EB) of the insect brain performs pivotal functions in controlling navigation. Input and output of the EB is provided by multiple classes of R-neurons (now referred to as ER-neurons) and columnar neurons which interact with each other in a stereotypical and spatially highly ordered manner. The developmental mechanisms that control the connectivity and topography of EB neurons are largely unknown. One indispensable prerequisite to unravel these mechanisms is to document in detail the sequence of events that shape EB neurons during their development. In this study, we analyzed the development of the Drosophila EB. In addition to globally following the ER-neuron and columnar neuron (sub)classes in the spatial context of their changing environment we performed a single cell analysis using the multi-color flip out (MCFO) system to analyze the developmental trajectory of ER-neurons at different pupal stages, young adults (4d) and aged adults (∼60d). We show that the EB develops as a merger of two distinct elements, a posterior and anterior EB primordium (prEBp and prEBa, respectively. ER-neurons belonging to different subclasses form growth cones and filopodia that associate with the prEBp and prEBa in a pattern that, from early pupal stages onward, foreshadows their mature structure. Filopodia of all ER-subclasses are initially much longer than the dendritic and terminal axonal branches they give rise to, and are pruned back during late pupal stages. Interestingly, extraneous branches, particularly significant in the dendritic domain, are a hallmark of ER-neuron structure in aged brains. Aging is also associated with a decline in synaptic connectivity from columnar neurons, as well as upregulation of presynaptic protein (Brp) in ER-neurons. Our findings advance the EB (and ER-neurons) as a favorable system to visualize and quantify the development and age-related decline of a complex neuronal circuitry. [Display omitted] • Growth cones and filopodia of ER-neurons were analyzed during development. • ER-neurons show type-specific characteristics that foreshadow their later morphology. • The dendritic domain of ER-neurons displays ectopic branches in aged brains. • Synaptic connectivity between ER-neurons and their targets declines in aged brains. [ABSTRACT FROM AUTHOR]

The ectoderm is the outermost of the three germ layers of the early embryo that arise during gastrulation. Once the germ layers are established, the complex interplay of cellular proliferation, differentiation, and migration results in organogenesis. The ectoderm is the progenitor of both the surface ectoderm and the neural ectoderm. Notably, the surface ectoderm develops into the epidermis and its associated appendages, nails, external exocrine glands, olfactory epithelium, and the anterior pituitary. Specification, development, and homeostasis of these organs demand a tightly orchestrated gene expression program that is often dictated by epigenetic regulation. In this review, we discuss the recent discoveries that have highlighted the importance of chromatin regulatory mechanisms mediated by transcription factors, histone and DNA modifications that aid in the development of surface ectodermal organs and maintain their homeostasis post-development. [Display omitted] • Chromatin regulatory mechanisms are inherently important for surface ectoderm organ development and homeostasis. • These mechanisms are mediated by transcription factors, histone, and DNA modifiers. • Recent studies have highlighted how signaling effectors, TFs, and chromatin modifiers converge to regulate key processes essential for tissue identity. [ABSTRACT FROM AUTHOR]

The evolutionary forces underlying the rapid evolution in sequences and functions of new genes remain a mystery. Adaptation by natural selection explains the evolution of some new genes. However, many new genes perform sex-biased functions that have rapidly evolved over short evolutionary time scales, suggesting that new gene evolution may often be driven by conflicting selective pressures on males and females. It is well established that such sexual conflict (SC) plays a central role in maintaining phenotypic and genetic variation within populations, but the role of SC in driving new gene evolution remains essentially unknown. This review explores the connections between SC and new gene evolution through discussions of the concept of SC, the phenotypic and genetic signatures of SC in evolving populations, and the molecular mechanisms by which SC could drive the evolution of new genes. We synthesize recent work in this area with a discussion of the case of Apollo and Artemis , two extremely young genes (<200,000 years) in Drosophila melanogaster , which offered the first empirical insights into the evolutionary process by which SC could drive the evolution of new genes. These new duplicate genes exhibit the hallmarks of sexually antagonistic selection: rapid DNA and protein sequence evolution, essential sex-specific functions in gametogenesis, and complementary sex-biased expression patterns. Importantly, Apollo is essential for male fitness but detrimental to female fitness, while Artemis is essential for female fitness but detrimental to male fitness. These sexually antagonistic fitness effects and complementary changes to expression, sequence, and function suggest that these duplicates were selected for mitigating SC, but that SC has not been fully resolved. Finally, we propose Sexual Conflict Drive as a self-driven model to interpret the rapid evolution of new genes, explain the potential for SC and sexually antagonistic selection to contribute to long-term evolution, and suggest its utility for understanding the rapid evolution of new genes in gametogenesis. [ABSTRACT FROM AUTHOR]

The article looks at the conversations and ideas exchanged between US and Mexican architects and planners in the early 1960s and their vision of redesigning the borderlands. Through a reading of Robert Evans Alexander's archival material (donated to Cornell University) and primary source material written by Guillermo Rossell, I argue that broader ideas of spatial justice influenced their conceptions of design. Moreover, Rossell brought to the table the idea that the border was a region and thus required a binational, regional design. The binational commission on planning developed in the midst of the Cold War and this was an element in their minds. And a part of this conversation, especially on the part of Mexican architects and planners, was development. Yet it was development through tourism, not industry. The article should be of interest to scholars working on the border, architecture and planning, development, tourism, and collaborative planning. • Collaborative binational planning along the US-Mexico borderlands. • Tourism as development. • Spatial justice in design. [ABSTRACT FROM AUTHOR]

If mitochondria are the powerhouses of the cell, then mitochondrial dynamics are the power grid that regulates how that energy output is directed and maintained in response to unique physiological demands. Fission and fusion dynamics are highly regulated processes that fine-tune the mitochondrial networks of cells to enable appropriate responses to intrinsic and extrinsic stimuli, thereby maintaining cellular and organismal homeostasis. These dynamics shape many aspects of an organism's healthspan including development, longevity, stress resistance, immunity, and response to disease. In this review, we discuss the latest findings regarding the mechanisms and roles of mitochondrial dynamics by focussing on the nematode Caenorhabditis elegans. Whole live-animal studies in C. elegans have enabled a true organismal-level understanding of the impact that mitochondrial dynamics play in homeostasis over a lifetime. [Display omitted] • Mitochondrial fission in C. elegans is mediated by DRP-1 and aided by FIS-1/2 and MFF-1/2. • Inner and outer membrane fusion is facilitated by EAT-3 and FZO-1, respectively. • Mitochondrial dynamics are critical for maintaining organismal homeostasis. • C. elegans is used to study dynamics during development, ageing, and disease. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) were first discovered in C. elegans as essential post-transcriptional regulators of gene expression. Since their initial discovery, miRNAs have been implicated in numerous areas of physiology and disease in all animals examined. In recent years, the C. elegans model continues to contribute important advances to all areas of miRNA research. Technological advances in tissue-specific miRNA profiling and genome editing have driven breakthroughs in understanding biological functions of miRNAs, mechanism of miRNA action, and regulation of miRNAs. In this review, we highlight these new C. elegans findings from the past five to seven years. [ABSTRACT FROM AUTHOR]

Selection acts differently on females and males due to differences in potential reproductive rates, driving the evolution of sex differences in traits, including growth and behaviour. Additionally, selection pressures vary during an individual's ontogeny, with growth being crucial in early developmental stages and reproduction during adulthood, leading to age- and sex-specific behavioural strategies. In this study, we investigated a sexually size dimorphic spider, the raft spider, Dolomedes fimbriatus , in which females are substantially larger than males. We repeatedly observed spiders from juvenile to adult stages, examining boldness, voracity towards prey and probability of attacking. Our findings revealed that females exhibited greater boldness, voracity and probability of attacking the simulated attacker than males. Notably, the observed behaviours changed during ontogeny, with sex differences in the magnitudes and directions of change, indicating distinct life history strategies between the sexes. Moreover, we detected positive associations between body mass or age and behavioural traits, supporting a proposed positive feedback loop between assets and behaviour. While mass and age were not significant confounding predictors in the analyses of sex differences in behaviour, some collinearity was present between sex, mass and age, so that their effects on behavioural differences between the sexes cannot be conclusively disentangled. Repeatability of behaviours was low but significant for boldness and probability of attacking, with similar estimates between the sexes. These results underscore the importance of considering sex-specific life history strategies in behavioural trait studies. • Females exhibited higher boldness, voraciousness and attack propensity than males. • The average levels of observed behaviours changed across ontogeny. • The magnitudes and directions of the change may reflect sex-specific strategies. • Repeatability of behaviours did not differ significantly between the sexes. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract is innervated by the enteric nervous system (ENS), a complex network of neurons and glial cells, also called the "second brain". Enteric glial cells, one of the major cell types in the ENS, are located throughout the entire gut wall. Accumulating evidence has demonstrated their critical requirement for gut physiology. Notably, recent studies have shown that enteric glial cells control new aspects of gut function such as regulation of intestinal stem cell behavior and immunity. In addition, the emergence of single-cell genomics technologies has revealed enteric glial cell heterogeneity and plasticity. In this review, we discuss established and emerging concepts regarding the roles of mammalian enteric glial cells and their heterogeneity in gut development, homeostasis, and regeneration. [ABSTRACT FROM AUTHOR]

The copepod species Acartia tonsa (Dana)(Crustacea) have the unique ability to induce quiescent embryonic dormancy if adverse environmental conditions occur; a characteristic shared by 41 other species belonging to the superfamily Centropagoida in the Calanoida order. However, the transcriptional changes characterizing this process are not known. Here, we compare the transcriptome of embryos in arrested quiescence with the normal development to identify pathways and differentially regulated transcripts involved in quiescent embryogenesis. Quiescence was induced by incubating eggs at 4 °C with anoxia for 26 h(hr), while eggs undergoing normal immediate development were incubated at 16.9 °C in normoxia for 7 h (where gastrulation occurs) or 14 h (where organogenesis occurs) before collecting for RNA extraction and analysis by RNA-sequencing. Results indicate that the expression profile of the quiescent embryo is not as different from the normal embryonic gastrulation as initially expected: None of the mapped transcripts is uniquely expressed in quiescence. Moreover, in quiescence a large proportion of the annotated transcripts display expression values halfway in-between the normal, immediate developmental stages of gastrulation and organogenesis. In depth comparison between the organogenesis stage and quiescent samples, reveal a high degree of divergence, confirming that a developmental arrest has been induced through quiescence. Specifically: Stress response transcripts are prominent in the quiescent phase with a transcript like the mammalian autophagy gene Sequestosome-1/p62 (SQSTM) being upregulated. The present analysis provides a better understanding of the molecular mechanisms characterizing the quiescent embryonic state of A. tonsa. [Display omitted] • Quiescent embryonic arrest of Acartia tonsa copepods was studied using RNA-sequencing and de novo transcriptome assembly. • Quiescence was induced by cold and anoxia and compared to gastrulation and organogenesis stages. • Quiescent embryonic arrest occurs in the gastrulation stage. • Quiescence is characterized by a profound stress response and induction of the autophagy gene Sequestosome (Sqstm). [ABSTRACT FROM AUTHOR]

A LIM homeodomain transcription factor Apterous (Ap) regulates embryonic and larval neurodevelopment in Drosophila. Although Ap is still expressed in the adult brain, it remains elusive whether Ap is involved in neurodevelopmental events in the adult brain because flies homozygous for ap mutations are usually lethal before they reach the adult stage. In this study, using adult escapers of ap knockout (KO) homozygotes, we examined whether the complete lack of ap expression affects the morphology of the mushroom body (MB) neurons and Pigment-dispersing factor (Pdf)-positive clock neurons in the adult brain. Although ap KO escapers showed severe structural defects of MB neurons, no clear morphological defects were found in Pdf-positive clock neurons. These results suggest that Ap in the adult brain is essential for the neurodevelopment of specific ap -positive neurons, but it is not necessarily involved in the development of all ap -positive neurons. • Drosophila apterous (ap) is essential for embryonic and larval neurodevelopment. • ap is expressed in the adult mushroom body (MB) and Pdf neurons. • ap knockout flies showed severe structural defects of MB neurons. • No morphological defects of Pdf neurons were detected in ap knockout flies. • ap does not necessarily regulate the development of all ap -positive neurons in adults. [ABSTRACT FROM AUTHOR]

We test the touchstones of economic rationality—utility maximization, stochastic dominance, and expected-utility maximization—of elite students in the U.S. and in Africa. The choices of most students in both samples are generally rationalizable, but the U.S. students' scores are substantially higher. Nevertheless, the development gap in economic rationality in incentivized risk choices between these future elites is much smaller than the difference in performance on a non-incentivized canonical cognitive ability test, often used as a proxy for economic decision-making ability in studies of economic development and growth. We argue for the importance of including consistency with economic rationality in studies of decision-making ability. [ABSTRACT FROM AUTHOR]

Smoking cigarettes during pregnancy is associated with adverse effects on infants including low birth weight, defective lung development, and skeletal abnormalities. Pregnant women are increasingly turning to vaping [use of electronic (e)-cigarettes] as a perceived safer alternative to cigarettes. However, nicotine disrupts fetal development, suggesting that like cigarette smoking, nicotine vaping may be detrimental to the fetus. To test the impact of maternal vaping on fetal lung and skeletal development in mice, pregnant dams were exposed to e-cigarette vapor throughout gestation. At embryonic day (E)18.5, vape exposed litter sizes were reduced, and some embryos exhibited growth restriction compared to air exposed controls. Fetal lungs were collected for histology and whole transcriptome sequencing. Maternally nicotine vaped embryos exhibited histological and transcriptional changes consistent with impaired distal lung development. Embryonic lung gene expression changes mimicked transcriptional changes observed in adult mouse lungs exposed to cigarette smoke, suggesting that the developmental defects may be due to direct nicotine exposure. Fetal skeletons were analyzed for craniofacial and long bone lengths. Nicotine directly binds and inhibits the Kcnj2 potassium channel which is important for bone development. The length of the maxilla, palatal shelves, humerus, and femur were reduced in vaped embryos, which was further exacerbated by loss of one copy of the Kcnj2 gene. Nicotine vapor exposed Kcnj2 KO/+ embryos also had significantly lower birth weights than unexposed animals of either genotype. Kcnj2 mutants had severely defective lungs with and without vape exposure, suggesting that potassium channels may be broadly involved in mediating the detrimental developmental effects of nicotine vaping. These data indicate that intrauterine nicotine exposure disrupts fetal lung and skeletal development likely through inhibition of Kcnj2. Nicotine vaping disrupts lung airway development, lung gene expression, craniofacial and long bone development, and increases sensitivity of skeletal consequences to variations in Kcnj2 function. [Display omitted] • Maternal e-cigarette use disrupts lung development. • Maternal nicotine vaping decreases expression of lung development genes. • Fetal exposure to nicotine vaping increases expression of cigarette smoking associated genes. • Embryonic exposure to e-cigarettes decreases the size of craniofacial and long bones. • Loss of one copy of Kcnj2 sensitizes embryos to the skeletal consequences of nicotine vaping. [ABSTRACT FROM AUTHOR]

General cellular aspects of skin development in vertebrates are presented with emphasis on the epidermis of sauropsids. Anamniote skin develops into a multilayered mucogenic and soft keratinized epidermis made of Intermediate Filament Keratins (IFKs) that is reinforced in most fish and few anurans by dermal bony and fibrous scales. In amniotes, the developing epidermis in contact with the amniotic fluid initially transits through a mucogenic phase recalling that of their anamniotes progenitors. A new gene cluster termed EDC (Epidermal Differentiation Complex) evolved in amniotes contributing to the origin of the stratum corneum. The EDC contains numerous genes coding for over 100 types of corneous proteins (CPs). In sauropsids 2–8 layers of embryonic epidermis accumulate soft keratins (IFKs) but do not form a compact corneous layer. The embryonic epidermis of reptiles and birds produces small amount of other, poorly known proteins in addition to IFKs and mucins. In the following development, a resistant corneous layer is formed underneath the embryonic epidermis that is shed before hatching. The definitive corneous epidermis of sauropsids is mainly composed of CBPs (Corneous beta proteins, formerly indicated as beta-keratins) derived from the EDC. CBPs belong to a gene sub-family of CPs unique for sauropsids, contain an inner amino acid region formed by beta-sheets, are rich in cysteine and glycine, and make most of the protein composition of scales, claws, beaks and feathers. In mammalian epidermis CPs missing the beta-sheet region are instead produced, and include loricrin, involucrin, filaggrin and various cornulins. Small amount of CPs accumulate in the 2–3 layers of mammalian embryonic epidermis and their appendages, that is replaced with the definitive corneous layers before birth. Differently from sauropsids, mammals utilize KAPs (keratin associated proteins) rich in cysteine and glycine for making the hard corneous material of hairs, claws, hooves, horns, and occasionally also scales. [Display omitted] • Amniote skin develops through an amphibious and then a terrestrial phase. • The mucogenic epidermis of fish and amphibians becomes corneous in amniotes. • In sauropsids the initially formed stratum corneum mainly produces Corneous Beta Proteins. • Genes for these proteins are localized in a locus known as Epidermal Differentiation Complex. • The accumulation of CBPs give rise to scales and other skin appendages including feathers in birds. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNA) transcripts are longer than 200 nt and are not translated into proteins. LncRNAs function in a wide variety of processes in plants and animals, but, perhaps because of their lower expression and conservation levels, plant lncRNAs had attracted less attention than protein-coding mRNAs. Now, recent studies have made remarkable progress in identifying lncRNAs and understanding their functions. In this review, we discuss a number of lncRNAs that have important functions in growth, development, reproduction, responses to abiotic stresses, and regulation of disease and insect resistance in plants. Additionally, we describe the known mechanisms of action of plant lncRNAs according to their origins within the genome. This review thus provides a guide for identifying and functionally characterizing new lncRNAs in plants. • LncRNAs that have functions in plant growth, responses to stresses were discussed. • The mechanisms of action of plant lncRNAs according to their origins were described. • A guide for identifying and functionally characterizing new lncRNAs in plants was provided. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 transmission to the fetal brain occurs at later stages of gestation in a human ACE2-KI mouse model. • SARS-CoV-2 targets blood vessel-comprising endothelial cells, neurons, glia, and choroid plexus cells in the fetal brain. •.Following in utero infection, developmental and neurological consequences are seen in neonatal mice. • COVID-19 infection in pregnant hACE2-KI mice replicates infection severity and effects seen in pregnant women. Whether or not SARS-CoV-2 can cross from mother to fetus during a prenatal infection has been controversial; however, recent evidence such as viral RNA detection in umbilical cord blood and amniotic fluid, as well as the discovery of additional entry receptors in fetal tissues suggests a potential for viral transmission to and infection of the fetus. Furthermore, neonates exposed to maternal COVID-19 during later development have displayed neurodevelopmental and motor skill deficiencies, suggesting the potential for consequential neurological infection or inflammation in utero. Thus, we investigated transmission potential of SARS-CoV-2 and the consequences of infection on the developing brain using human ACE2 knock-in mice. In this model, we found that viral transmission to the fetal tissues, including the brain, occurred at later developmental stages, and that infection primarily targeted male fetuses. In the brain, SARS-CoV-2 infection largely occurred within the vasculature, but also within other cells such as neurons, glia, and choroid plexus cells; however, viral replication and increased cell death were not observed in fetal tissues. Interestingly, early gross developmental differences were observed between infected and mock-infected offspring, and high levels of gliosis were seen in the infected brains 7 days post initial infection despite viral clearance at this time point. In the pregnant mice, we also observed more severe COVID-19 infections, with greater weight loss and viral dissemination to the brain, compared to non-pregnant mice. Surprisingly, we did not observe an increase in maternal inflammation or the antiviral IFN response in these infected mice, despite showing clinical signs of disease. Overall, these findings have concerning implications regarding neurodevelopment and pregnancy complications of the mother following prenatal COVID-19 exposure. [ABSTRACT FROM AUTHOR]

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]

Historically, the empirical study of phenotypic diversification has fallen into two rough camps; (1) "structuralist approaches" focusing on developmental constraint, bias, and innovation (with evo-devo at the core); and (2) "adaptationist approaches" focusing on adaptation, and natural selection. Whilst debates, such as that surrounding the proposed "Extended" Evolutionary Synthesis, often juxtapose these two positions, this review focuses on the grey space in between. Specifically, here I present a novel analysis of structuralism which enables us to take a more nuanced look at the motivations behind the structuralist and adaptationist positions. This makes clear how the two approaches can conflict, and points of potential commensurability. The review clarifies (a) the value of the evo-devo approach to phenotypic diversity, but also (b) how it properly relates to other predominant approaches to the same issues in evolutionary biology more broadly. [ABSTRACT FROM AUTHOR]

The high costs of predation and the opportunity costs associated with predator avoidance are likely to select for flexibility in the development of antipredator responses based on local socioecological conditions. As group size is hypothesized to vary across populations as a function of predation risk, the development of antipredator behaviours throughout ontogeny may be influenced by the size of an individual's social group. Here, we explore the development of alarm call responses in wild vervet monkeys living at the Samara Game Reserve, South Africa. Vervet monkeys at this site live in relatively large social groups, and adult responses to alarms have previously shown less uniformity than in other sites where group sizes are smaller. We presented monkeys playback recordings of terrestrial alarm calls produced by individuals of different age–sex classes. We then videorecorded and scored the responses of receivers along an ordinal maturity scale. We used a mixed-effects ordinal logistic regression model within a Bayesian framework to explore how response intensity is affected by the age–sex of the caller, and the age of receivers. Our analysis showed that younger monkeys (<2 years old) exhibit strong evasive responses to call stimuli, regardless of the age–sex class of the caller. The intensity of these responses decreases with age, with responses to nonalarm calls decreasing earlier in development than responses to alarm calls. Adult responses to alarm calls in this population are as likely to be characterized by a general increase in vigilance as they are to consist of an evasive response. We suggest that responses in younger individuals at Samara are mediated by generalized startle responses to loud, plosive noises. Development of more specific responses throughout ontogeny is likely to be dependent on learning from adult models, whose milder responses reflect local socioecological conditions specific to Samara. • Response intensity to playbacks decreased with age. • Individuals under 2 years of age responded overtly to all playback stimuli. • Adults were more likely to respond to alarm playbacks with vigilance. • Response intensity to control calls decreased earlier compared to alarm calls. • Some evidence that adults responded less overtly to alarms produced by adult males. [ABSTRACT FROM AUTHOR]

Understanding how retinal progenitor cells (RPCs) give rise to the variety of neural cell types of the retina has been a question of major interest over the last few decades. While environmental cues and transcription factor networks have been shown to control specific cell fate decisions, how RPCs alter fate output over time to control proper histogenesis remains poorly understood. In recent years, the identification of "temporal identity factors (TIFs)", which control RPC competence states to ensure that the right cell types are produced at the right time, has contributed to increasing our understanding of temporal patterning in the retina. Here, we review the different TIFs identified to date in the mammalian retina and discuss the underlying mechanisms by which they are thought to operate. We conclude by speculating on how identification of temporal patterning mechanisms might support the development of new therapeutic approaches against visual impairments. [ABSTRACT FROM AUTHOR]

The ability of a single genome to express multiple phenotypes is key to understanding social systems. In social insects, caste and task-specific morphologies are typically determined by the social environment during larval development. Here, we used the bumble bee Bombus impatiens to examine the social regulation of body size and caste by manipulating the identity (queen/worker) and the number of caretakers tending for the brood. Eggs of females and males were kept in cages with (1) a queen, (2) one worker, (3) three workers or (4) 10 workers. We measured larval weight, developmental duration and the resulting caste (in females) throughout the development of >2000 individuals. We found differences in larval mass when reared by varying number of workers, but not when reared by a single worker compared to a queen. Additionally, in contrast with previous findings in Bombus terrestris , none of the female eggs reared by workers developed into queens, indicating the existence of multiple mechanisms for caste determination in bumble bees. Adult males were slightly larger than workers and took longer to develop in the presence of the queen. The hypothesis that the queen's presence manipulates female development and caste was not supported by our data. Overall, we suggest that body size in B. impatiens is determined by the number of caretakers and is likely mediated by the amount of provision. • Body size and development in B. impatiens are determined by the number of caretakers. • Body size and development do not depend on the caretaker identity. • Body size is likely mediated by the amount of provision provided to larvae. • The queen is unlikely to be the sole regulator of gyne production. • Caste determination mechanisms likely vary across bumble bee species. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

Technological advances have driven many recent advances in developmental biology. Light sheet imaging can reveal single-cell dynamics in living three-dimensional tissues, whereas single-cell genomic methods open the door to a complete catalogue of cell types and gene expression states. An equally powerful but complementary set of approaches are also becoming available to define development processes from the bottom up. These synthetic approaches aim to reconstruct the minimal developmental patterns, signaling processes, and gene networks that produce the basic set of developmental operations: spatial polarization, morphogen interpretation, tissue movement, and cellular memory. In this review we discuss recent approaches at the intersection of synthetic biology and development, including synthetic circuits to deliver and record signaling stimuli and synthetic reconstitution of pattern formation on multicellular scales. [ABSTRACT FROM AUTHOR]

Over the last decade, the combination of genetics, transcriptomic and proteomic approaches yielded substantial insights into the mechanisms behind the synthesis and breakdown of energy stores in the model organisms. The fruit fly Drosophila melanogaster has been particularly useful to unravel genetic regulations of energy metabolism. Despite the considerable evolutionary distance between humans and flies, the energy storage organs, main metabolic pathways, and even their genetic regulations remained relatively conserved. Glycogen and fat are universal energy reserves used in all animal phyla and several of their endocrine regulators, such as the insulin pathway, are highly evolutionarily conserved. Nevertheless, some of the factors inducing catabolism of energy stores have diverged significantly during evolution. Moreover, even within a single insect species, D. melanogaster , there are substantial developmental and context-dependent variances in the regulation of energy stores. These differences include, among others, the endocrine pathways that govern the catabolic events or the predominant fuel which is utilized for the given process. For example, many catabolic regulators that control energy reserves in adulthood seem to be largely dispensable for energy mobilization during development. In this review, we focus on a selection of the most important catabolic regulators from the group of peptide hormones (Adipokinetic hormone, Corazonin), catecholamines (octopamine), steroid hormones (20-hydroxyecdysone), and other factors (extracellular adenosine, regulators of lipase Brummer). We discuss their roles in the mobilization of energy reserves for processes such as development through non-feeding stages, flight or starvation survival. Finally, we conclude with future perspectives on the energy balance research in the fly model. • Many metabolic regulations are evolutionarily conserved between Drosophila and human. • Glycogen and triacylglycerol are universal energy sources. • Catabolism of reserves is required for embryogenesis, metamorphosis, starvation survival, immunity, and flight. • Catabolism is governed by peptides, catecholamines, steroids, and extracellular adenosine. [ABSTRACT FROM AUTHOR]

The organ of Corti, located in the cochlea within the inner ear is the receptor organ for hearing. It converts auditory signals into neuronal action potentials that are transmitted to the brain for further processing. The mature organ of Corti consists of a variety of highly differentiated sensory cells that fulfil unique tasks in the processing of auditory signals. The actin and microtubule cytoskeleton play essential function in hearing, however so far, more attention has been paid to the role of actin. Microtubules play important roles in maintaining cellular structure and intracellular transport in virtually all eukaryotic cells. Their functions are controlled by interactions with a large variety of microtubule-associated proteins (MAPs) and molecular motors. Current advances show that tubulin posttranslational modifications, as well as tubulin isotypes could play key roles in modulating microtubule properties and functions in cells. These mechanisms could have various effects on the stability and functions of microtubules in the highly specialised cells of the cochlea. Here, we review the current understanding of the role of microtubule-regulating mechanisms in the function of the cochlea and their implications for hearing, which highlights the importance of microtubules in the field of hearing research. [ABSTRACT FROM AUTHOR]

Bearded capuchin monkeys at Fazenda Boa Vista, Piauí, Brazil older than 8 years routinely crack palm nuts with a stone hammer and anvil. An embodied, perception–action stance hypothesizes that monkeys' improving skill at this task is enabled by learning affordances of spatial and force relations produced with objects. Affordances are individual-relative opportunities for action that may change across development. We evaluated predictions linking behaviours with nuts and stones and body mass to success at nut cracking in young bearded capuchins (1.3–6.3 years old) and adults over three annual observation periods. Behaviours with nuts and stones reflected the monkeys' learning affordances for cracking; body mass constrained affordances for cracking. For each period in which they were observed, individuals were assigned to novice, intermediate or expert classes in accord with their success at cracking nuts. Novices did not crack nuts, despite striking them with stones. Body mass was modestly associated with intermediates', but not experts', likelihood of cracking a nut. Experts exhibited higher proportions of manipulation devoted to positioning nuts on the anvil and shorter bouts of cracking than intermediates; intermediates exhibited greater variability in these variables than experts or novices. The strongest classification model predicting individuals' assignments to skill class with 89% accuracy combined average bout duration and the ratio of manipulation devoted to positioning to other manipulation. The findings suggest practise using the body-pus-tool system for cracking palm nuts supports affordance learning and results in gradual mastery of this skill and that changing body mass plays a small role in this process. • Most monkeys <7 years old did not have adult (expert) skill at cracking nuts. • Body mass had little to no effect on monkeys' skill at cracking nuts. • Experts cracked nuts in short bouts and relatively frequently positioned the nut. • Less skilled monkeys used long bouts and varied duration and action more over bouts. • Monkeys slowly learn affordances of the body-plus-tool system for nut cracking. [ABSTRACT FROM AUTHOR]

The continued integrity of biological systems depends on a balance between interdependent elements at the molecular, cellular, and organismal levels. This is particularly true for the generation of ribosomes, which influence almost every aspect of cell and organismal biology. Ribosome biogenesis (RiBi) is an energetically demanding process that involves all three RNA polymerases, numerous RNA processing factors, chaperones, and the coordinated expression of 79–80 ribosomal proteins (r-proteins). Work over the last several decades has revealed that the dynamic regulation of ribosome production represents a major mechanism by which cells maintain homeostasis in response to changing environmental conditions and acute stress. More recent studies suggest that cells and tissues within multicellular organisms exhibit dramatically different levels of ribosome production and protein synthesis, marked by the differential expression of RiBi factors. Thus, distinct bottlenecks in the RiBi process, downstream of rRNA transcription, may exist within different cell populations of multicellular organisms during development and in adulthood. This review will focus on our current understanding of the mechanisms that link the complex molecular process of ribosome biogenesis with cellular and organismal physiology. We will discuss diverse topics including how different steps in the RiBi process are coordinated with one another, how MYC and mTOR impact RiBi, and how RiBi levels change between stem cells and their differentiated progeny. In turn, we will also review how regulated changes in ribosome production itself can feedback to influence cell fate and function. [ABSTRACT FROM AUTHOR]

Bacterial cytokinesis starts with the polymerization of the tubulin-like FtsZ, which forms the cell division scaffold. SepF aligns FtsZ polymers and also acts as a membrane anchor for the Z-ring. While in most bacteria cell division takes place at midcell, during sporulation of Streptomyces many septa are laid down almost simultaneously in multinucleoid aerial hyphae. The genomes of streptomycetes encode two additional SepF paralogs, SflA and SflB, which can interact with SepF. Here we show that the sporogenic aerial hyphae of sflA and sflB mutants of Streptomyces coelicolor frequently branch, a phenomenon never seen in the wild-type strain. The branching coincided with ectopic localization of DivIVA along the lateral wall of sporulating aerial hyphae. Constitutive expression of SflA and SflB largely inhibited hyphal growth, further correlating SflAB activity to that of DivIVA. SflAB localized in foci prior to and after the time of sporulation-specific cell division, while SepF co-localized with active septum synthesis. Foci of FtsZ and DivIVA frequently persisted between adjacent spores in spore chains of sflA and sflB mutants, at sites occupied by SflAB in wild-type cells. Taken together, our data show that SflA and SflB play an important role in the control of growth and cell division during Streptomyces development. • Discovery of the SepF-like proteins SflA and SflB as novel cell division control proteins in Streptomyces. • Over-expression of SflA or SflB reduces growth and prevents attachment of surface-grown colonies. • Deletion of the genes for SflA or SflB results in unique premature germination of spores in the spore chains of Streptomyces. • Premature germination is caused by the ectopic localization of DivIVA in sflA and sflB mutants. • SflA and SflB ensure the disassembly of DivIVA and FtsZ after completion of cell division. [ABSTRACT FROM AUTHOR]

[Display omitted] • Critical windows exist: microbiota depletion in early life has enduring effects on the gut microbiota. • Early-life microbiota disruption induces subtle changes in circulating immune cells. • Evidence of sex and time-dependent effects on myelin-related gene expression. • Microglial morphology in the basolateral amygdala is altered by early-life microbiota disruption. • Effects on anxiety-like and compulsive behaviours occur in a sex- and time-dependent manner. Numerous studies have emphasised the importance of the gut microbiota during early life and its role in modulating neurodevelopment and behaviour. Epidemiological studies have shown that early-life antibiotic exposure can increase an individual's risk of developing immune and metabolic diseases. Moreover, preclinical studies have shown that long-term antibiotic-induced microbial disruption in early life can have enduring effects on physiology, brain function and behaviour. However, these studies have not investigated the impact of targeted antibiotic-induced microbiota depletion during critical developmental windows and how this may be related to neurodevelopmental outcomes. Here, we addressed this gap by administering a broad-spectrum oral antibiotic cocktail (ampicillin, gentamicin, vancomycin, and imipenem) to mice during one of three putative critical windows: the postnatal (PN; P2-9), pre-weaning (PreWean; P12-18), or post-weaning (Wean; P21-27) developmental periods and assessed the effects on physiology and behaviour in later life. Our results demonstrate that targeted microbiota disruption during early life has enduring effects into adolescence on the structure and function of the caecal microbiome, especially for antibiotic exposure during the weaning period. Further, we show that microbial disruption in early life selectively alters circulating immune cells and modifies neurophysiology in adolescence, including altered myelin-related gene expression in the prefrontal cortex and altered microglial morphology in the basolateral amygdala. We also observed sex and time-dependent effects of microbiota depletion on anxiety-related behavioural outcomes in adolescence and adulthood. Antibiotic-induced microbial disruption had limited and subtle effects on social behaviour and did not have any significant effects on depressive-like behaviour, short-term working, or recognition memory. Overall, this study highlights the importance of the gut microbiota during critical windows of development and the subtle but long-term effects that microbiota-targeted perturbations can have on brain physiology and behaviour. [ABSTRACT FROM AUTHOR]

Brown algae are complex multicellular eukaryotes whose cells possess a cell wall, which is an important structure that regulates cell size and shape. Alginate and fucose-containing sulfated polysaccharides (FCSPs) are two carbohydrate types that have major roles in influencing the mechanical properties of the cell wall (i.e. increasing or decreasing wall stiffness), which in turn regulate cell expansion, division, adhesion, and other processes; however, how brown algal cell wall structure regulates its mechanical properties, and how this relationship influences cellular growth and organismal development, is not well-understood. This chapter is focused on reviewing what we currently know about how the roles of alginates and FCSPs in brown algal developmental processes, as well as how they influence the structural and mechanical properties of cell walls. Additionally, we discuss how brown algal mutants may be leveraged to learn more about the underlying mechanisms that regulate cell wall structure, mechanics, and developmental processes, and finally we propose questions to guide future research with the use of emerging technologies. [ABSTRACT FROM AUTHOR]

Liver organogenesis is a complex process. Although many signaling pathways and key factors have been identified during liver development, little is known about the regulation of late liver development, especially liver maturation. As a transcriptional repressor, SPEN has been demonstrated to interact with lncRNAs and transcription factors to participate in X chromosome inactivation, neural development, and lymphocyte differentiation. General disruption of SPEN results in embryonic lethality accompanied by hampered liver development in mice. However, the function of SPEN in embryonic liver development has not been reported. In this study, we demonstrate that SPEN is required for hepatocyte maturation using hepatocyte-specific disruption of SPEN with albumin-Cre-mediated knockout. SPEN expression was upregulated in hepatocytes along with liver development in mice. The deletion of the SPEN gene repressed hepatic maturation, mainly by a decrease in hepatic metabolic function and disruption of hepatocyte zonation. Additional experiments revealed that transcription factors which control hepatocyte maturation were strongly downregulated in SPEN-deficient hepatocytes, especially Hnf4α. Furthermore, restoration of Hnf4α levels partially rescued the immature state of hepatocytes caused by SPEN gene deletion. Taken together, these results reveal an unexpected role of SPEN in liver maturation. • SPEN expression was upregulated in hepatocytes during liver development in mice. • Hepatocyte SPEN ablation repressed hepatic maturation, manifested bythe impairment of hepatic metabolic function and disruption of hepatocyte zonation. • Transcription factors which control hepatocyte maturation were strongly downregulated in SPEN-deficient hepatocytes, especially Hnf4α. • Restoration of Hnf4α levels partially rescued the immature state of hepatocytes caused by SPEN deletion. [ABSTRACT FROM AUTHOR]

During early embryogenesis, as cells divide in the developing embryo, the size of intracellular organelles generally decreases to scale with the decrease in overall cell size. Organelle size scaling is thought to be important to establish and maintain proper cellular function, and defective scaling may lead to impaired development and disease. However, how the cell regulates organelle size and organization are largely unanswered questions. In this review, we summarize the process of size scaling at both the cell and organelle levels and discuss recently discovered mechanisms that regulate this process during early embryogenesis. In addition, we describe how some recently developed techniques and Xenopus as an animal model can be used to investigate the underlying mechanisms of size regulation and to uncover the significance of proper organelle size scaling and organization. [ABSTRACT FROM AUTHOR]

In many taxa, variations in the early social context are well known to influence the expression of a suite of behaviours later in life. For species living temporarily in groups, relatively few studies have examined how the ontogenetic change in the social context experienced by individuals during their transition from social to solitary influences their responses to environmental variation. It can be hypothesized that the presence of conspecifics during the gregarious phase may constrain the expression of any behavioural changes in response to external variations that would be detrimental to group cohesion and reduce the benefits associated with social life. In this study, we investigated the interplay between early social experience, satiation and ontogeny in the development of aggressive behaviours in juveniles of the solitary spider Agelena labyrinthica. First, we exposed spiderlings to a period of social isolation of similar duration at different ages, while others were continuously reared socially. Second, we examined how feeding influences the onset of agonistic interactions in spiderlings reared in isolation or socially. When spiders were socially deprived, we found that aggressive behaviour towards siblings increased both when they experienced isolation at a later developmental stage and when they were fed. This was in contrast to spiders maintained in groups, which, regardless of their age and whether they were fed or not, remained tolerant. Overall, our study suggests that changes in the social environment during ontogeny set the context for the expression of behavioural plasticity that prepares individuals for living alone. • Late social isolation during ontogeny increases aggression in spiderlings. • Food intake in socially isolated spiderlings increases aggression. • Spiderlings reared socially are less sensitive to environmental conditions. • The expression of behavioural plasticity depends on the social context. [ABSTRACT FROM AUTHOR]

It is known that all living organisms are mortal. For many decades, the main interest of researchers has been focused on the investigation of proliferation, differentiation and other fundamental cellular processes, completely ignoring the understanding of the mechanisms of cell elimination. Since the 60s–70s of the last century, a systematic study of cell death began, which is currently one of the most rapidly developing areas of biomedicine. Since this field of research is very wide, in these short notes we tried to discuss the hottest, but not all, topics that are of interest to many of our colleagues. [ABSTRACT FROM AUTHOR]

In the last decades, the post-translational modification system by covalent attachment of the SUMO polypeptide to proteins has emerged as an essential mechanism controlling virtually all the physiological processes in the eukaryotic cell. This includes vertebrate development. In the nervous system, SUMO plays crucial roles in synapse establishment and it has also been linked to a variety of neurodegenerative diseases. However, to date, the involvement of the modification of specific targets in key aspects of nervous system development, like patterning and differentiation, has remained largely elusive. A number of recent works confirm the participation of target-specific SUMO modification in critical aspects of nervous system development. Here, we review pioneering and new findings demonstrating the essential role SUMO plays in neurogenesis and other facets of neurodevelopment, which will help to precisely understand the variety of mechanisms SUMO utilizes to control most fundamental processes in the cell. [ABSTRACT FROM AUTHOR]

Enhancers and promoters are cis -regulatory elements that control gene expression. Enhancers are activated in a cell type-, tissue-, and condition-specific manner to stimulate promoter function and transcription. Zebrafish have emerged as a powerful animal model for examining the activities of enhancers derived from various species through transgenic enhancer assays, in which an enhancer is coupled with a minimal promoter. However, the efficiency of minimal promoters and their compatibility with multiple developmental and regeneration enhancers have not been systematically tested in zebrafish. Thus, we assessed the efficiency of six minimal promoters and comprehensively interrogated the compatibility of the promoters with developmental and regeneration enhancers. We found that the fos minimal promoter and Drosophila synthetic core promoter (DSCP) yielded high rates of leaky expression that may complicate the interpretation of enhancer assays. Notably, the adenovirus E1b promoter, the zebrafish lepb 0.8-kb (P0.8) and lepb 2-kb (P2) promoters, and a new zebrafish synthetic promoter (ZSP) that combines elements of the E1b and P0.8 promoters drove little or no ectopic expression, making them suitable for transgenic assays. We also found significant differences in compatibility among specific combinations of promoters and enhancers, indicating the importance of promoters as key regulatory elements determining the specificity of gene expression. Our study provides guidelines for transgenic enhancer assays in zebrafish to aid in the discovery of functional enhancers regulating development and regeneration. [Display omitted] • fos and DSCP minimal promoters drive high rates of leaky expression. • Developmental enhancers are preferentially compatible with E1b promoter. • Regeneration enhancers are preferentially compatible with P0.8 and P2 promoters. • ZSP promoter is highly compatible with developmental and regeneration enhancers. [ABSTRACT FROM AUTHOR]

Fascin expression has commonly been observed in certain subtypes of breast cancer, where its expression is associated with poor clinical outcome. However, its role in normal mammary gland development has not been elucidated. Here, we used a fascin knockout mouse model to assess its role in normal mammary gland morphogenesis and lactation. Fascin knockout was not embryonically lethal, and its effect on the litter size or condition at birth was minimal. However, litter survival until the weaning stage significantly depended on fascin expression solely in the nursing dams. Accordingly, pups that nursed from fascin−/− dams had smaller milk spots in their abdomen, suggesting a lactation defect in the nursing dams. Mammary gland whole-mounts of pregnant and lactating fascin−/− mice showed significantly reduced side branching and alveologenesis. Despite a typical composition of basal, luminal, and stromal subsets of mammary cells and normal ductal architecture of myoepithelial and luminal layers, the percentage of alveolar progenitors (ALDH+) in fascin−/− epithelial fraction was significantly reduced. Further in-depth analyses of fascin−/− mammary glands showed a significant reduction in the expression of Elf5 , the master regulator of alveologenesis, and a decrease in the activity of its downstream target p-STAT5. In agreement, there was a significant reduction in the expression of the milk proteins, whey acidic protein (WAP), and β-casein in fascin−/− mammary glands. Collectively, our data demonstrate, for the first time, the physiological role of fascin in normal mammary gland lactogenesis, an addition that could reveal its contribution to breast cancer initiation and progression. [Display omitted] [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR)—composed of multiple complexes, including mTOR complex 1/2 (mTORC1/2)—is a serine-threonine kinase that regulates embryonic development. The transcription factor, hypoxia-inducible factor-1α (HIF-1α), is also involved in embryonic development. As the relationship between mTOR and HIF-1α during embryonic development remains unclear, we investigated the relationship between the two using ex vivo submandibular salivary gland organ cultures. When the expression of HIF-1α increased under hypoxic conditions (1% O 2), the expression of mTOR signaling pathway-related proteins decreased. Conversely, when the expression of HIF-1α decreased, the expression of mTOR signaling pathway-related proteins increased. These results indicate a strong relationship between HIF-1α and the mTOR signaling pathway. For the first time, we clarified that HIF-1α negatively regulates the mTOR signaling pathway and suppresses salivary gland development under 1% O 2 using small molecules. Our research provides new insights into the relationship between HIF-1α and the mTOR signaling pathway in embryonic organ development. • ・Salivary gland development is suppressed under 1% O 2. • ・HIF-1α and mTOR signaling pathway have a strong relationship in salivary gland development. • ・HIF-1α negatively regulates mTOR signaling pathway under 1% O 2 in salivary gland development. [ABSTRACT FROM AUTHOR]

TGF-β plays a prominent role as an inducer of epithelial-mesenchymal transitions (EMTs) during development and wound healing and in disease conditions such as fibrosis and cancer. During these processes EMT occurs together with changes in cell proliferation, differentiation, communication, and extracellular matrix remodeling that are orchestrated by multiple signaling inputs besides TGF-β. Chief among these inputs is RAS-MAPK signaling, which is frequently required for EMT induction by TGF-β. Recent work elucidated the molecular basis for the cooperation between the TGF-β-SMAD and RAS-MAPK pathways in the induction of EMT in embryonic, adult and carcinoma epithelial cells. These studies also provided direct mechanistic links between EMT and progenitor cell differentiation during gastrulation or intra-tumoral fibrosis during cancer metastasis. These insights illuminate the nature of TGF-β driven EMTs as part of broader processes during development, fibrogenesis and metastasis. [ABSTRACT FROM AUTHOR]

Gametes are cells that have the unique ability to give rise to new individuals as well as transmit (epi)genetic information across generations. Generation of functionally competent gametes, oocytes and sperm cells, depends to some extent on several fundamental processes that occur during fetal development. Direct studies on human fetal germ cells remain hindered by ethical considerations and inaccessibility to human fetal material. Therefore, the majority of our current knowledge of germ cell development still comes from an invaluable body of research performed using different mammalian species. During the last decade, our understanding of human fetal germ cells has increased due to the successful use of human pluripotent stem cells to model aspects of human early gametogenesis and advancements on single-cell omics. Together, this has contributed to determine the cell types and associated molecular signatures in the developing human gonads. In this review, we will put in perspective the knowledge obtained from several mammalian models (mouse, monkey, pig). Moreover, we will discuss the main events during human fetal (female) early gametogenesis and how the dysregulation of this highly complex and lengthy process can link to infertility later in life. [ABSTRACT FROM AUTHOR]

Due to advancements in ultrasound techniques, the focus of antenatal ultrasound screening is moving towards the first trimester of pregnancy. The early first trimester however remains in part, a 'black box', due to the size of the developing embryo and the limitations of contemporary scanning techniques. Therefore there is a need for images of early anatomical developmental to improve our understanding of this area. By using new imaging techniques, we can not only obtain better images to further our knowledge of early embryonic development, but clear images of embryonic and fetal development can also be used in training for e.g. sonographers and fetal surgeons, or to educate parents expecting a child with a fetal anomaly. The aim of this review is to provide an overview of the past, present and future techniques used to capture images of the developing human embryo and fetus and provide the reader newest insights in upcoming and promising imaging techniques. The reader is taken from the earliest drawings of da Vinci, along the advancements in the fields of in utero ultrasound and MR imaging techniques towards high-resolution ex utero imaging using Micro-CT and ultra-high field MRI. Finally, a future perspective is given about the use of artificial intelligence in ultrasound and new potential imaging techniques such as synchrotron radiation-based CT to increase our knowledge regarding human development. [ABSTRACT FROM AUTHOR]

Mammalian corneal development is a multistep process, including formation of the corneal epithelium (CE), endothelium and stroma during embryogenesis, followed by postnatal stratification of the epithelial layers and continuous renewal of the epithelium to replace the outermost corneal cells. Here, we employed the Cre- loxP system to conditionally deplete Pax6 proteins in two domains of ocular cells, i.e., the ocular surface epithelium (cornea, limbus and conjunctiva) (OSE) or postnatal CE via K14-cre or Aldh3-cre , respectively. Earlier and broader inactivation of Pax6 in the OSE resulted in thickened OSE with CE and limbal cells adopting the conjunctival keratin expression pattern. More restricted depletion of Pax6 in postnatal CE resulted in an abnormal cornea marked by reduced epithelial thickness despite increased epithelial cell proliferation. Immunofluorescence studies revealed loss of intermediate filament Cytokeratin 12 and diffused expression of adherens junction components, together with reduced tight junction protein, Zonula occludens-1. Furthermore, the expression of Cytokeratin 14, a basal cell marker in apical layers, indicates impaired differentiation of CE cells. Collectively, our data demonstrate that Pax6 is essential for maintaining proper differentiation and strong intercellular adhesion in postnatal CE cells, whereas limbal Pax6 is required to prevent the outgrowth of conjunctival cells to the cornea. [Display omitted] • Transcription factor Pax6 is required for postnatal corneal development. • Pax6-deficient ocular surface ectoderm develops exclusively into conjunctiva. • Conjunctivalisation of the cornea leads to the loss of the limbal region. • Pax6-deficient corneal epithelial cells are defective in intercellular adhesion. • Loss of intercellular adhesion is accompanied by differentiation defects. [ABSTRACT FROM AUTHOR]

• First characterization of the immune cell profile of the developing rat brain from embryonic day 20 to postnatal day 16. • The profile of peripheral immune cells in the brain is developmentally and regionally regulated. • Mimic of peripheral viral infection causes influx of additional select immune cells into the developing brain. • The developmental shift in the peripheral immune cell population is consistent with a change from reactive to surveilling. Little is known about the peripheral immune cell (PIC) profile of the developing brain despite growing appreciation for these cells in the mature nervous system. To address this gap, the PIC profile, defined as which cells are present, where they are located, and for how long, was examined in the developing rat using spectral flow cytometry. Select regions of the rat brain (cerebellum, hippocampus, and hypothalamus) were examined at embryonic day 20, and postnatal days 0, 7 and 16. At their peak (E20), PICs were most abundant in the cerebellum, then the hippocampus and hypothalamus. Within the PIC pool, monocytes were most prevalent in all regions and time points, and shifted from being majority classical at E20 to non-classical by PN7. T cells increased over time, and shifted from majority cytotoxic to T-helper cells by PN7. This suggests the PIC profile transitions from reactive to adaptive and surveilling in the second postnatal week. NK cells and mast cells increased temporarily, and mast cells were restricted to the hippocampus and hypothalamus, suggesting they may play a specific role in the development of those regions. Mimicking a viral infection by administration of Poly I:C increased the influx of PICs into the neonatal brain, particularly of NK cells and in the case of males only, non-classical monocytes. This work provides a map for researchers as they study immune cell contributions to healthy and pathological brain development. [ABSTRACT FROM AUTHOR]

Revealing the organizing principles of developing neural networks is a difficult but significant task in neuroscience. As a creature with a rather compact and well-studied neural network, C. elegans is an ideal subject for neuroscience study. However, the researches on its developing neural network remain challenging. The changes in specific properties of neural network across development may uncover part of its principles. Motif is a typical structure property that can be well applied to various complex networks. Here, we study the motif changes in C. elegans neural network across development. By counting the occurrence number of all three-node subgraph motif structures in its neural network at different stages of C. elegans development, along with those in corresponding random networks, we determine which of these structures are motifs for C. elegans , finding out the regular changes of motifs during its development. Combined with the potential function of these subgraph motifs and synaptic information, we gain insight into the organizing principle of neural network during development, which may increase our understanding of neuroscience and inspire the construction of artificial neural network. • The numbers of occurrences of all three-node subgraph motif structures in C. elegans neural network during development are counted. • By comparing with the results in corresponding random networks, which structure is motif in developmental C. elegans neural network is determined. • The average connection strength information within motifs is gathered. • The organizing principle of developmental neural network in C. elegans that tends to increase the significance of signal processing is acquired. [ABSTRACT FROM AUTHOR]

How our brains have developed to perform the many complex functions that make us human has long remained a question of great interest. Over the last few decades, many scientists from a wide range of fields have tried to answer this question by aiming to uncover the mechanisms that regulate the development of the human neocortex. They have approached this on different scales, focusing microscopically on individual cells all the way up to macroscopically imaging entire brains within living patients. In this review we will summarise these key findings and how they fit together. [ABSTRACT FROM AUTHOR]

Maternal behavior experienced in early life provides essential scaffolding to infant psychobiology with life-long effects on neurobiological and behavioral outcomes. However, infants are not passive recipients of caregiving. Evidence in rodents suggests that pups actively contribute to dam-pup interactions by soliciting maternal care with auditory, tactile, and hormonal cues. The limited bedding and nesting material (LBN) rearing manipulation induces changes in maternal care that have been attributed to maternal stress caused by the low-resource environment. The goal of the current study was to determine whether LBN also alters pup cues for maternal behavior, with implications for the mechanism of LBN-induced effects. Rat dams and pups were randomly assigned to LBN or Control rearing conditions on postnatal day (P) 0–6 and pups were fostered to the same or different condition on P6–13. LBN increased pup-directed maternal behaviors measured through 24 h monitoring using machine learning based automated analysis. LBN altered several pup cues known to affect maternal behavior including reducing pup core body temperature, reducing body weight, and altering pup vocalizations on P6 and P12. P6–13 LBN-exposed pups had elevated serum testosterone, which positively correlated with maternal licking and grooming. LBN reduced pup movement between nest attendance onset and the start of nursing, which was negatively related to dam nursing latency and contributed to longer nursing latency in LBN dams. P0–6 pup exposure to LBN also led to longer nest attendance bouts and shorter licking and grooming bouts on P7 and P9, suggesting lasting effects of LBN on pups. These data demonstrate that LBN changes pup behavioral and hormonal signals consistent with eliciting more maternal care, contributing to augmented pup-directed behaviors. This bidirectional interplay may be a critical mechanism involved in the lasting effects of early life environments. • Limited bedding (LBN) increased maternal pup-directed behaviors. • LBN, dam behavior, and pup age affected pup body temperature. • Home cage pup movement was reduced by LBN and predicted dam nursing latency. • LBN increased pup serum testosterone and was correlated with licking and grooming. • LBN effects on pups are consistent with eliciting more maternal care. [ABSTRACT FROM AUTHOR]