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Sensory organs must develop alongside the skull within which they are largely encased, and this relationship can manifest as the skull constraining the organs, organs constraining the skull, or organs constraining one another in relative size. How this interplay between sensory organs and the developing skull plays out during the evolution of sensory diversity; however, remains unknown. Here, we examine the developmental sequence of the cochlea, the organ responsible for hearing and echolocation, in species with distinct diet and echolocation types within the ecologically diverse bat super-family Noctilionoidea. We found the size and shape of the cochlea largely correlates with skull size, with exceptions of Pteronotus parnellii, whose high duty cycle echolocation (nearly constant emission of sound pulses during their echolocation process allowing for detailed information gathering, also called constant frequency echolocation) corresponds to a larger cochlear and basal turn, and Monophyllus redmani, a small-bodied nectarivorous bat, for which interactions with other sensory organs restrict cochlea size. Our findings support the existence of developmental constraints, suggesting that both developmental and anatomical factors may act synergistically during the development of sensory systems in noctilionoid bats., (© 2023 American Association for Anatomy.)

Tooth classes are an innovation that has contributed to the evolutionary success of mammals. However, our understanding of the mechanisms by which tooth classes diversified remain limited. We use the evolutionary radiation of noctilionoid bats to show how the tooth developmental program evolved during the adaptation to new diet types. Combining morphological, developmental and mathematical modeling approaches, we demonstrate that tooth classes develop through independent developmental cascades that deviate from classical models. We show that the diversification of tooth number and size is driven by jaw growth rate modulation, explaining the rapid gain/loss of teeth in this clade. Finally, we mathematically model the successive appearance of tooth buds, supporting the hypothesis that growth acts as a key driver of the evolution of tooth number and size. Our work reveal how growth, by tinkering with reaction/diffusion processes, drives the diversification of tooth classes and other repeated structure during adaptive radiations., (© 2023. Springer Nature Limited.)

Background: Through the evolution of novel wing structures, bats (Order Chiroptera) became the only mammalian group to achieve powered flight. This achievement preceded the massive adaptive radiation of bats into diverse ecological niches. We investigate some of the developmental processes that underlie the origin and subsequent diversification of one of the novel membranes of the bat wing: the plagiopatagium, which connects the fore- and hind limb in all bat species., Results: Our results suggest that the plagiopatagium initially arises through novel outgrowths from the body flank that subsequently merge with the limbs to generate the wing airfoil. Our findings further suggest that this merging process, which is highly conserved across bats, occurs through modulation of the programs controlling the development of the periderm of the epidermal epithelium. Finally, our results suggest that the shape of the plagiopatagium begins to diversify in bats only after this merging has occurred., Conclusions: This study demonstrates how focusing on the evolution of cellular processes can inform an understanding of the developmental factors shaping the evolution of novel, highly adaptive structures., (© 2023. The Author(s).)

Stem cell regulation plays a crucial role during development and homeostasis. Here, an essential source of Wnts from Gli1 + stem/progenitor cells was identified in the murine molar. Loss of Wnt production in Gli1 + apical stem/progenitor cells led to loss of Axin2 at the root apex, mis-regulation of SOX9, loss of BMP and Hh signaling, and truncation of root development. In the absence of Wnt signals, the root epithelium lost its integrity and epithelial identity. This phenotype could be partially mimicked by loss of Sox9 in the Gli1 population. Stabilization of Wnt signaling in the apical papilla led to rapid unordered differentiation of hard tissues and fragmentation of the epithelial root sheath. Wnt signaling from Gli1 + stem/progenitor cells, therefore, orchestrates root development, coordinating mesenchymal and epithelial interactions via SOX9 to regulate stem/progenitor cell expansion and differentiation. Our results demonstrate that disparate stem/progenitor cell populations are unified in their fundamental signaling interactions., Competing Interests: Conflict of interests A.S.T. is also affiliated with Charles University, Czech Republic., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In the echidna, after development in utero, the egg is laid in the pouch and incubated for 10 days. During this time, the fetuses develop an egg tooth and caruncle to help them hatch. Using rare and unprecedented access to limited echidna pre- and post-hatching tissues, development of the egg tooth and caruncle were assessed by micro-CT, histology and immunofluorescence. Unlike therian tooth germs that develop by placode invagination, the echidna egg tooth developed by evagination, similar to the first teeth in some reptiles and fish. The egg tooth ankylosed to the premaxilla, rather than forming a tooth root with ligamentous attachment found in other mammals, with loss of the egg tooth associated with high levels of activity odontoclasts and apoptosis. The caruncle formed as a separate mineralisation from the adjacent nasal capsule, and as observed in birds and turtles, the nasal region epithelium on top of the nose expressed markers of cornification. Together, this highlights that the monotreme egg tooth shares many similarities with typical reptilian teeth, suggesting that this tooth has been conserved from a common ancestor of mammals and reptiles., Competing Interests: Declaration of competing interest The authors have no financial interests and no competing interests declared., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A jaw joint between the squamosal and dentary is a defining feature of mammals and is referred to as the temporomandibular joint (TMJ) in humans. Driven by changes in dentition and jaw musculature, this new joint evolved early in the mammalian ancestral lineage and permitted the transference of the ancestral jaw joint into the middle ear. The fossil record demonstrates the steps in the cynodont lineage that led to the acquisition of the TMJ, including the expansion of the dentary bone, formation of the coronoid process, and initial contact between the dentary and squamosal. From a developmental perspective, the components of the TMJ form through tissue interactions of muscle and skeletal elements, as well as through interaction between the jaw and the cranial base, with the signals involved in these interactions being both biomechanical and biochemical. In this review, we discuss the development of the TMJ in an evolutionary context. We describe the evolution of the TMJ in the fossil record and the development of the TMJ in embryonic development. We address the formation of key elements of the TMJ and how knowledge from developmental biology can inform our understanding of TMJ evolution., (© 2022 The Authors. Evolution & Development published by Wiley Periodicals LLC.)

Mammal forelimbs are highly diverse, ranging from the elongated wing of a bat to the stout limb of the mole. The mammal forelimb has been a long-standing system for the study of early developmental patterning, proportional variation, shape change, and the reduction of elements. However, most of this work has been performed in mice, which neglects the wide variation present across mammal forelimbs. This review emphasizes the critical role of non-model systems in limb evo-devo and highlights new emerging models and their potential. We discuss the role of gene networks in limb evolution, and touch on functional analyses that lay the groundwork for further developmental studies. Mammal limb evo-devo is a rich field, and here we aim to synthesize the findings of key recent works and the questions to which they lead., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: To compare the uniqueness of human dentition in both orthodontically treated and untreated populations and evaluate the reliability of bitemark analysis., Materials and Methods: A total of 1464 maxillary and mandibular casts were fabricated from orthodontically treated and nontreated population. After careful examination of the study teeth, 326 nontreated maxillary cast (Group 1), 333 nontreated mandibular cast (Group 2), 336 orthodontically treated maxillary cast (Group 3), and 320 orthodontically treated mandibular casts (Group 4) were selected for the analysis. For uniformity, the sample size of 320 was selected from each group for comparison., Results: The arch width was a major cause of variance. In Group 1, only 6.87% of similarity rate was seen, whereas in Group 3, the match rate increased to 55% showing similarity. In Group 2, only 1.87% similarity and Group 4 showed 42.7% match rate., Conclusion: The human dentition may be unique, but it loses its uniqueness once any dental treatment is carried out., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Oral and Maxillofacial Pathology.)

Bats are incredibly diverse, both morphologically and taxonomically. Bats are the only mammalian group to have achieved powered flight, an adaptation that is hypothesized to have allowed them to colonize various and diverse ecological niches. However, the lack of fossils capturing the transition from terrestrial mammal to volant chiropteran has obscured much of our understanding of bat evolution. Over the last 20 years, the emergence of evo-devo in non-model species has started to fill this gap by uncovering some developmental mechanisms at the origin of bat diversification. In this review, we highlight key aspects of studies that have used bats as a model for morphological adaptations, diversification during adaptive radiations, and morphological novelty. To do so, we review current and ongoing studies on bat evolution. We first investigate morphological specialization by reviewing current knowledge about wing and face evolution. Then, we explore the mechanisms behind adaptive diversification in various ecological contexts using vision and dentition. Finally, we highlight the emerging work into morphological novelties using bat wing membranes.

Meckel's cartilage was first described by the German anatomist Johann Friedrich Meckel the Younger in 1820 from his analysis of human embryos. Two hundred years after its discovery this paper follows the development and largely transient nature of the mammalian Meckel's cartilage, and its role in jaw development. Meckel's cartilage acts as a jaw support during early development, and a template for the later forming jaw bones. In mammals, its anterior domain links the two arms of the dentary together at the symphysis while the posterior domain ossifies to form two of the three ear ossicles of the middle ear. In between, Meckel's cartilage transforms to a ligament or disappears, subsumed by the growing dentary bone. Several human syndromes have been linked, directly or indirectly, to abnormal Meckel's cartilage formation. Herein, the evolution, development and fate of the cartilage and its impact on jaw development is mapped. The review focuses on developmental and cellular processes that shed light on the mechanisms behind the different fates of this cartilage, examining the control of Meckel's cartilage patterning, initiation and maturation. Importantly, human disorders and mouse models with disrupted Meckel's cartilage development are highlighted, in order to understand how changes in this cartilage impact on later development of the dentary and the craniofacial complex as a whole. Finally, the relative roles of tissue interactions, apoptosis, autophagy, macrophages and clast cells in the removal process are discussed. Meckel's cartilage is a unique and enigmatic structure, the development and function of which is starting to be understood but many interesting questions still remain., (Copyright © 2020 Svandova, Anthwal, Tucker and Matalova.)

Mammals articulate their jaws using a novel joint between the dentary and squamosal bones. In eutherian mammals, this joint forms in the embryo, supporting feeding and vocalisation from birth. In contrast, marsupials and monotremes exhibit extreme altriciality and are born before the bones of the novel mammalian jaw joint form. These mammals need to rely on other mechanisms to allow them to feed. Here, we show that this vital function is carried out by the earlier developing, cartilaginous incus of the middle ear, abutting the cranial base to form a cranio-mandibular articulation. The nature of this articulation varies between monotremes and marsupials, with juvenile monotremes retaining a double articulation, similar to that of the fossil mammaliaform Morganucodon , while marsupials use a versican-rich matrix to stabilise the jaw against the cranial base. These findings provide novel insight into the evolution of mammals and the changing relationship between the jaw and ear., Competing Interests: NA, JF, SJ, MR, AT No competing interests declared, (© 2020, Anthwal et al.)

The novel mammalian jaw joint, known in humans as the temporomandibular joint or TMJ, is cushioned by a fibrocartilage disc. This disc is secondarily absent in therian mammals that have lost their dentition, such as giant anteaters and some baleen whales. The disc is also absent in all monotremes. However, it is not known if the absence in monotremes is secondary to the loss of dentition, or if it is an ancestral absence. We use museum held platypus and echidna histological sections to demonstrate that the developing monotreme jaw joint forms a disc primordium that fails to mature and become separated from the mandibular condyle. We then show that monotreme developmental anatomy is similar to that observed in transgenic mouse mutants with reduced cranial musculature. We therefore suggest that the absence of the disc on monotremes is a consequence of the changes in jaw musculature associated with the loss of adult teeth. Taken together, these data indicate that the ancestors of extant monotremes likely had a jaw joint disc, and that the disc evolved in the last common ancestor of all mammals., (Copyright © 2020 Anthwal and Tucker.)

In this question and answer article we discuss how evolution shapes morphology (the shape and pattern of our bodies) but also how learning about morphology, and specifically how that morphology arises during development, can shed light on mechanisms that might allow change during evolution. For this we concentrate on recent findings from our lab on how the middle ear has formed in mammals.

Introduction: Gender estimation from dismembered human body parts and skeletal remains in cases of mass disasters, explosions, and assaults cases is an imperative element of any medico-legal investigations and has been a major challenge for forensic scientists., Aim: The aim of the present study was to estimate the gender by using index and ring finger length ratio, hand and foot index along with the correlation of both the hand and foot index to determine the vital role of all the indices in establishing gender identity., Materials and Methods: A descriptive cross-sectional study was done on 300 subjects (150 males and 150 females). Various anthropometric measurements like hand length, hand breadth and hand index, Index Finger Length (IFL), Ring Finger Length (RFL) and IFL/RFL ratio as well as foot length, foot breadth and foot index were estimated in millimeters (mm) with the help of sliding-anthropometric caliper. The data was analysed using independent t-test and Pearson correlation coefficient test. A probability value (p) of ≤ 0.05 was considered statistically significant., Results: The index and ring finger ratio was found to be higher in females as compared to males. The hand and foot index was more in males than in females. The index and ring finger length ratio, hand and foot index between males and females was found to be statistically significant for both hands and feet. A statistically significant correlation was determined between hand indexes versus foot index., Conclusion: This study can be useful to establish the gender of a dismembered hand or foot when subjected for medicolegal examination.

A key transformation in mammalian ear evolution was incorporation of the primary jaw joint of premammalian synapsids into the definitive mammalian middle ear of living mammals. This evolutionary transition occurred in two-steps, starting with a partial or "transitional" mammalian middle ear in which the ectotympanic and malleus were still connected to the mandible by an ossified Meckel's Cartilage (MC), as observed in many Mesozoic mammals. This was followed by MC breakdown, freeing the ectotympanic and the malleus from the mandible and creating the definitive mammalian middle ear. Here we report novel findings on the role of chondroclasts in MC breakdown, shedding light on how therian mammals lost MC connecting the ear to the jaw. Genetic or pharmacological loss of clast cells in mice and opossums leads to persistence of embryonic MC beyond juvenile stages, with MC ossification in mutant mice. The persistent MC causes a distinctive postnatal groove on the mouse dentary. This morphology phenocopies the ossified MC and Meckelian groove observed in Mesozoic mammals. Clast cell recruitment to MC is not observed in reptiles, where MC persists as a cartilaginous structure. We hypothesize that ossification of MC is an ancestral feature of mammaliaforms, and that a shift in the timing of clast cell recruitment to MC prior to its ossification is a key developmental mechanism for the evolution of the definitive mammalian middle ear in extant therians., Competing Interests: Author information The authors declare no competing financial interests.

Multiple mammalian lineages independently evolved a definitive mammalian middle ear (DMME) through breakdown of Meckel's cartilage (MC). However, the cellular and molecular drivers of this evolutionary transition remain unknown for most mammal groups. Here, we identify such drivers in the living marsupial opossum Monodelphis domestica , whose MC transformation during development anatomically mirrors the evolutionary transformation observed in fossils. Specifically, we link increases in cellular apoptosis and TGF-BR2 signalling to MC breakdown in opossums. We demonstrate that a simple change in TGF-β signalling is sufficient to inhibit MC breakdown during opossum development, indicating that changes in TGF-β signalling might be key during mammalian evolution. Furthermore, the apoptosis that we observe during opossum MC breakdown does not seemingly occur in mouse, consistent with homoplastic DMME evolution in the marsupial and placental lineages., (© 2017 The Author(s).)

How teeth are replaced during normal growth and development has long been an important question for comparative and developmental anatomy. Non-standard model animals have become increasingly popular in this field due to the fact that the canonical model laboratory mammal, the mouse, develops only one generation of teeth (monophyodonty), whereas the majority of mammals possess two generations of teeth (diphyodonty). Here we used the straw-coloured fruit bat (Eidolon helvum), an Old World megabat, which has two generations of teeth, in order to observe the development and replacement of tooth germs from initiation up to mineralization stages. Our morphological study uses 3D reconstruction of histological sections to uncover differing arrangements of the first and second-generation tooth germs during the process of tooth replacement. We show that both tooth germ generations develop as part of the dental lamina, with the first generation detaching from the lamina, leaving the free edge to give rise to a second generation. This separation was particularly marked at the third premolar locus, where the primary and replacement teeth become positioned side by side, unconnected by a lamina. The position of the replacement tooth, with respect to the primary tooth, varied within the mouth, with replacements forming posterior to or directly lingual to the primary tooth. Development of replacement teeth was arrested at some tooth positions and this appeared to be linked to the timing of tooth initiation and the subsequent rate of development. This study adds an additional species to the growing body of non-model species used in the study of tooth replacement, and offers a new insight into the development of the diphyodont condition., (© 2016 Anatomical Society.)

The mammalian ear is a complex structure divided into three main parts: the outer; middle; and inner ear. These parts are formed from all three germ layers and neural crest cells, which have to integrate successfully in order to form a fully functioning organ of hearing. Any defect in development of the outer and middle ear leads to conductive hearing loss, while defects in the inner ear can lead to sensorineural hearing loss. This review focuses on the development of the parts of the ear involved with sound transduction into the inner ear, and the parts largely ignored in the world of hearing research: the outer and middle ear. The published data on the embryonic origin, signalling, genetic control, development and timing of the mammalian middle and outer ear are reviewed here along with new data showing the Eustachian tube cartilage is of dual embryonic origin. The embryonic origin of some of these structures has only recently been uncovered (Science, 339, 2013, 1453; Development, 140, 2013, 4386), while the molecular mechanisms controlling the growth, structure and integration of many outer and middle ear components are hardly known. The genetic analysis of outer and middle ear development is rather limited, with a small number of genes often affecting either more than one part of the ear or having only very small effects on development. This review therefore highlights the necessity for further research into the development of outer and middle ear structures, which will be important for the understanding and treatment of conductive hearing loss., (© 2015 Anatomical Society.)

Background: The variation in mandibular morphology of mammals reflects specialisations for different diets. Omnivorous and carnivorous mammals posses large mandibular coronoid processes, while herbivorous mammals have proportionally smaller or absent coronoids. This is correlated with the relative size of the temporalis muscle that forms an attachment to the coronoid process. The role of this muscle attachment in the development of the variation of the coronoid is unclear., Results: By comparative developmental biology and mouse knockout studies, we demonstrate here that the initiation and growth of the coronoid are two independent processes, with initiation being intrinsic to the ossifying bone and growth dependent upon the extrinsic effect of muscle attachment. A necessary component of the intrinsic patterning is identified as the paired domain transcription factor Pax9. We also demonstrate that Sox9 plays a role independent of chondrogenesis in the growth of the coronoid process in response to muscle interaction., Conclusions: The mandibular coronoid process is initiated by intrinsic factors, but later growth is dependent on extrinsic signals from the muscle. These extrinsic influences are hypothesised to be the basis of the variation in coronoid length seen across the mammalian lineage.

The ventral hypothalamus acts to integrate visceral and systemic information to control energy balance. The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3) is required for pancreatic β-cell development and has been implicated in neuronal development in the hypothalamus. Here, we demonstrate that early embryonic hypothalamic inactivation of Ngn3 (also known as Neurog3) in mice results in rapid post-weaning obesity that is associated with hyperphagia and reduced energy expenditure. This obesity is caused by loss of expression of Pomc in Pomc- and Cart-expressing (Pomc/Cart) neurons in the arcuate nucleus, indicating an incomplete specification of anorexigenic first order neurons. Furthermore, following the onset of obesity, both the arcuate and ventromedial hypothalamic nuclei become insensitive to peripheral leptin treatment. This conditional mouse mutant therefore represents a novel model system for obesity that is associated with hyperphagia and underactivity, and sheds new light upon the roles of Ngn3 in the specification of hypothalamic neurons controlling energy balance.

Having three ossicles in the middle ear is one of the defining features of mammals. All reptiles and birds have only one middle ear ossicle, the stapes or columella. How these two additional ossicles came to reside and function in the middle ear of mammals has been studied for the last 200 years and represents one of the classic example of how structures can change during evolution to function in new and novel ways. From fossil data, comparative anatomy and developmental biology it is now clear that the two new bones in the mammalian middle ear, the malleus and incus, are homologous to the quadrate and articular, which form the articulation for the upper and lower jaws in non-mammalian jawed vertebrates. The incorporation of the primary jaw joint into the mammalian middle ear was only possible due to the evolution of a new way to articulate the upper and lower jaws, with the formation of the dentary-squamosal joint, or TMJ in humans. The evolution of the three-ossicle ear in mammals is thus intricately connected with the evolution of a novel jaw joint, the two structures evolving together to create the distinctive mammalian skull., (© 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.)

The neuroendocrine hypothalamus regulates a spectrum of essential biological processes and underlies a range of diseases from growth failure to obesity. While the exploration of hypothalamic function has progressed well, knowledge of hypothalamic development is poor. In particular, very little is known about the processes underlying the genesis and specification of the neurons in the arcuate and ventromedial nuclei. Recent studies demonstrate that the proneural basic helix-loop-helix transcription factor Mash1 is required for neurogenesis and neuronal subtype specification in the ventral hypothalamus. We demonstrate here that Ngn3, another basic helix-loop-helix transcription factor, is expressed in mitotic progenitors in the arcuate and ventromedial hypothalamic regions of mouse embryos from embryonic days 9.5-17.5. Genetic fate mapping and loss of function studies in mice demonstrate that Ngn3+ progenitors contribute to subsets of POMC, NPY, TH and SF1 neurons and is required for the specification of these neuronal subtypes in the ventral hypothalamus. Interestingly, while Ngn3 promotes the development of arcuate POMC and ventromedial SF1 neurons, it inhibits the development of NPY and TH neurons in the arcuate nuclei. Given the opposing roles of POMC and NPY neurons in regulating food intake, these results indicate that Ngn3 plays a central role in the generation of neuronal populations controlling energy homeostasis in mice., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The evolution of the novel mammalian jaw articulation has resulted in an increased complexity of the dentary bone, reflecting the multiple roles it now fulfils as the primary bone of the mandible. Signalling through the Tgf-beta type II receptor is important in the development and patterning of the proximal dentary processes, especially the angular process, and secondary cartilages. We show that expression of Tgf-beta2 is associated with the developing angular process, and that the connective tissue marker Scleraxis is co-expressed with Tgf-beta2. Scleraxis expression is lost around the angular process of Tgfbr2 conditional knockouts and Tgf-beta signalling can induce Scleraxis expression in explant culture. Induction of secondary cartilages in explant culture can be prevented by inhibition of Tgf-beta signalling. This study suggests that the proper development of the processes and their secondary cartilages relies on both Tgf-beta signalling and mechanical forces working in concert.