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A model of somite formation in vertebrates is presented in which a biochemical wave selects alternating regions of vertebra and somite production. It does so by imposing expression of a relevant gene in the underlying DNA in the form of a relaxation oscillation. [ABSTRACT FROM AUTHOR]

Amphioxus represents the most basally divergent group in chordates and probably the best extant proxy to the ancestor of all chordates including vertebrates. The amphioxus, or lancelets, are benthic filter feeding marine animals and their interest as a model in research is due to their phylogenetic position and their anatomical and genetic stasis throughout their evolutionary history. From the first works in the 19th century to the present day, enormous progress is made mainly favored by technical development at different levels, from spawning induction and husbandry techniques, through techniques for studies of gene function or of the role of different signalling pathways through embryonic development, to functional genomics techniques. Together, these advances foretell a plethora of interesting developments in the world of research with the amphioxus model. Here, the discovery and development of amphioxus as a superb model organism in evolutionary and evolutionary‐developmental biology are reviewed. Cephalochordates (i.e., amphioxus, or lancelet) are invertebrate chordates, extremely conserved at anatomical and genomic levels, making them animals of choice for EvoDevo studies aimed at understanding the evolutionary events that gave rise to vertebrates. Here, the discovery and the development of amphioxus as a model for evolutionary biology is reviewed. [ABSTRACT FROM AUTHOR]

Abstract The expression of the TGF-β protein Nodal on the left side of vertebrate embryos is a determining event in the development of internal-organ asymmetry. We present a mathematical model for the control of the expression of Nodal and its antagonist Lefty consisting entirely of realistic elementary reactions. We analyze the model in the absence of Lefty and find a wide range of parameters over which bistability (two stable steady states) is observed, with one stable steady state a low-Nodal state corresponding to the right-hand developmental fate, and the other a high-Nodal state corresponding to the left. We find that bistability requires a transcription factor containing two molecules of phosphorylated Smad2. A numerical survey of the full model, including Lefty, shows the effects of Lefty on the potential for bistability, and on the conditions that lead to the system reaching one or the other steady state. [ABSTRACT FROM AUTHOR]

Somitogenesis, the sequential formation of a periodic pattern along the anteroposterior axis of vertebrate embryos, is one of the most obvious examples of the segmental patterning processes that take place during embryogenesis and also one of the major unresolved events in developmental biology. In this paper, we investigate the effect of diffusion on pattern formation use a modified two dimensional model which can be used to explain somitogenesis during embryonic development. This model is suitable for exploring a design space of somitogenesis and can explain many aspects of somitogenesis that previous models cannot. In the present paper, by analyzing the local linear stability of the equation, we acquired the conditions of Hopf bifurcation and Turing bifurcation. In addition, the amplitude equation near the Turing bifurcation point is obtained by using the methods of multi-scale expansion and symmetry analysis. By analyzing the stability of the amplitude equation, we know that there are various complex phenomena, including Spot pattern, mixture of spot–stripe patterns and labyrinthine. Finally, numerical simulation are given to verify the correctness of our theoretical results. Somitogenesis occupies an important position in the process of biological development, and as a pattern process can be used to investigate many aspects of embryogenesis. Therefore, our study helps greatly to cell differentiation, gene expression and embryonic development. What is more, it is of great significance for the diagnosis and treatment of human diseases to study the related knowledge of model biology. [ABSTRACT FROM AUTHOR]

In the vertebrate embryo, the eyes develop from optic vesicles that grow laterally outward from the brain tube and contact the overlying surface ectoderm. Within the region of contact, each optic vesicle and the surface ectoderm thicken to form placodes, which then invaginate to create the optic cup and lens pit, respectively. Eventually, the optic cup becomes the retina, while the lens pit closes to form the lens vesicle. Here, we review current hypotheses for the physical mechanisms that create these structures and present novel three-dimensional computer (finite-element) models to illustrate the plausibility and limitations of these hypotheses. Taken together, experimental and numerical results suggest that the driving forces for early eye morphogenesis are generated mainly by differential growth, actomyosin contraction, and regional apoptosis, with morphology mediated by physical constraints provided by adjacent tissues and extracellular matrix. While these studies offer new insight into the mechanics of eye development, future work is needed to better understand how these mechanisms are regulated to precisely control the shape of the eye. [ABSTRACT FROM AUTHOR]

Robust protocols for directed differentiation of human pluripotent cells are required to determine whether mechanisms operating in model organisms are relevant to our own development. Recent work in vertebrate embryos has identified neuromesodermal progenitors as a bipotent cell population that contributes to paraxial mesoderm and spinal cord. However, precise protocols for in vitro differentiation of human spinal cord progenitors are lacking. Informed by signalling in amniote embryos, we show here that transient dual-SMAD inhibition, together with retinoic acid (dSMADi-RA), provides rapid and reproducible induction of human spinal cord progenitors from neuromesodermal progenitor-like cells. Using CRISPR-Cas9 to engineer human embryonic stem cells with a GFP-reporter for neuromesodermal progenitor-associated gene Nkx1.2 we facilitate selection of this cell population. RNA-sequencing was then used to identify human and conserved neuromesodermal progenitor transcriptional signatures, to validate this differentiation protocol and to reveal new pathways/processes in human neural differentiation. This optimised protocol, novel reporter line and transcriptomic data are useful resources with which to dissect molecular mechanisms regulating human spinal cord generation and allow the scaling-up of distinct cell populations for global analyses, including proteomic, biochemical and chromatin interrogation. [ABSTRACT FROM AUTHOR]

During early embryonic development, the vertebrate main body axis is segmented from head-to-tail into somites. Somites emerge sequentially from the presomitic mesoderm (PSM) as a consequence of oscillatory waves of genetic activity, called somitogenesis waves. Here, we discuss the implications of the dynamic patterns of early X-Delta-2 expression in the prospective somites (somitomeres) of Xenopus laevis. We report that right somitomeres normally emerge before left to form chiral structures (i.e. structures having clockwise or counter-clockwise handedness). From our observations, we infer that somitogenesis waves are normally counter-clockwise spirals, a novel dynamic mechanism for the control of handedness development in Xenopus. We propose that the same mechanism could control handedness development in all vertebrate embryos, providing a dynamical basis for the current asymmetric molecular transport model for generating left-right asymmetry. [ABSTRACT FROM AUTHOR]

Abstract: Skeletal progenitors are derived from resident limb bud mesenchymal cells of the vertebrate embryos. However, it remains poorly understood if they represent stem cells, progenitors, or multipotent mesenchymal stromal cells (MSC). Derived‐MSC of different adult tissues under in vitro experimental conditions can differentiate into the same cellular lineages that are present in the limb. Here, comparing non‐cultured versus cultured mesenchymal limb bud cells, we determined the expression of MSC‐associated markers, the in vitro differentiation capacity and their gene expression profile. Results showed that in freshly isolated limb bud mesenchymal cells, the proportion of cells expressing Sca1, CD44, CD105, CD90, and CD73 is very low and a low expression of lineage‐specific genes was observed. However, recently seeded limb bud mesenchymal cells acquired Sca1 and CD44 markers and the expression of the key differentiation genes Runx2 and Sox9, while Scx and Pparg genes decreased. Also, their chondrogenic differentiation capacity decreased through cellular passages while the osteogenic increased. Our findings suggest that the modification of the cell adhesion process through the in vitro method changed the limb mesenchymal cell immunophenotype leading to the expression and maintenance of common MSC‐associated markers. These findings could have a significant impact on MSC study and isolation strategy because they could explain common variations observed in the MSC immunophenotype in different tissues. [ABSTRACT FROM AUTHOR]

During early vertebrate embryogenesis, bone morphogenetic proteins (BMPs) belonging to the transforming growth factor‐β (TGF‐β) family of growth factors play a central role in dorsal–ventral (DV) patterning of embryos, while other growth factors such as Wnt and fibroblast growth factor (FGF) family members regulate formation of the anterior–posterior (AP) axis. Although the establishment of body plan is thought to require coordinated formation of the DV and AP axes, the mechanistic details underlying this coordination are not well understood. Here, we show that a Xenopus homologue of zbtb14 plays an essential role in the regulation of both DV and AP patterning during early Xenopus development. We show that overexpression of Zbtb14 promotes neural induction and inhibits epidermal differentiation, thereby regulating DV patterning. In addition, Zbtb14 promotes the formation of posterior neural tissue and suppresses anterior neural development. Consistent with this, knock‐down experiments show that Zbtb14 is required for neural development, especially for the formation of posterior neural tissues. Mechanistically, Zbtb14 reduces the levels of phosphorylated Smad1/5/8 to suppress BMP signaling and induces an accumulation of β‐Catenin to promote Wnt signaling. Collectively, these results suggest that Zbtb14 plays a crucial role in the formation of DV and AP axes by regulating both the BMP and Wnt signaling pathways during early Xenopus embryogenesis. [ABSTRACT FROM AUTHOR]

Over the last thirty years, fish models, such as the zebrafish and medaka, have become essential to pursue developmental studies and model human disease. Community efforts have led to the generation of wide collections of mutants, a complete sequence of their genomes, and the development of sophisticated genetic tools, enabling the manipulation of gene activity and labelling and tracking of specific groups of cells during embryonic development. When combined with the accessibility and optical clarity of fish embryos, these approaches have made of them an unbeatable model to monitor developmental processes in vivo and in real time. Over the last few years, live-imaging studies in fish have provided fascinating insights into tissue morphogenesis and organogenesis. This review will illustrate the advantages of fish models to pursue morphogenetic studies by highlighting the findings that, in the last decade, have transformed our understanding of eye morphogenesis. [ABSTRACT FROM AUTHOR]

During tissue development, the morphogenesis of epithelial sheets is regulated by many factors, including mechanical force, although the underlying mechanisms remain largely unknown. In the pharyngeal region of the vertebrate embryo, endodermal epithelium is reiteratively folded outward to form pharyngeal pouches, making partitions between the pharyngeal arches. Ripply3, encoding a member of the Ripply family of adaptor proteins, is required for the pouch formation posterior to the 2nd pharyngeal pouch. In this study, we found that the expression of mouse Ripply3 was specifically activated in accordance with the bending of the endodermal epithelium during the pouch formation. In Ripply3‐deficient embryos, a continuous monolayer of the endodermal epithelium was not maintained posterior to the 2nd pharyngeal pouch. Corresponding to the endodermal region of the deformed epithelium, the activated form of Integrin β1, which was localized at the basal side of the epithelial cells in the wild‐type embryos, was not persistently observed in the mutants. On the other hand, cell proliferation and apoptotic cell death in the endoderm were not obviously affected by the Ripply3 deficiency. Significantly, Ripply3 expressed in cultured cells was found to be preferentially accumulated in the focal adhesions, which are Integrin‐mediated adhesive contact sites transmitting mechanical force between the extracellular matrix and attached cells. Furthermore, Ripply3 promoted the maturation of focal adhesions in these cells. Thus, Ripply3 appears to have been activated to enhance the connection between the extracellular matrix and endodermal epithelial cells, as a mechanism to resist the mechanical stress generated during the bending of the epithelial sheets. [ABSTRACT FROM AUTHOR]

The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates. We further test the hypothesis by investigating the role of cWnt signaling during early patterning along the A/P axis of the hemichordate Saccoglossus kowalevskii. We have cloned and investigated the expression of the complete Wnt ligand and Frizzled receptor complement of S. kowalevskii during early development along with many secreted Wnt modifiers. Eleven of the 13 Wnt ligands are ectodermally expressed in overlapping domains, predominantly in the posterior, and Wnt antagonists are localized predominantly to the anterior ectoderm in a pattern reminiscent of their distribution in vertebrate embryos. Overexpression and knockdown experiments, in combination with embryological manipulations, establish the importance of cWnt signaling for repression of anterior fates and activation of mid-axial ectodermal fates during the early development of S. kowalevskii. However, surprisingly, terminal posterior fates, defined by posterior Hox genes, are unresponsive to manipulation of cWnt levels during the early establishment of the A/P axis at late blastula and early gastrula. We establish experimental support for a conserved role of Wnt signaling in the early specification of the A/P axis during deuterostome body plan diversification, and further build support for an ancestral role of this pathway in early evolution of the bilaterian A/P axis. We find strong support for a role of cWnt in suppression of anterior fates and promotion of mid-axial fates, but we find no evidence that cWnt signaling plays a role in the early specification of the most posterior axial fates in S. kowalevskii. This posterior autonomy may be a conserved feature of early deuterostome axis specification. [ABSTRACT FROM AUTHOR]

For decades, in situ hybridization methods have been essential tools for studies of vertebrate development and disease, as they enable qualitative analyses of mRNA expression in an anatomical context. Quantitative mRNA analyses typically sacrifice the anatomy, relying on embryo microdissection, dissociation, cell sorting and/or homogenization. Here, we eliminate the trade-off between quantitation and anatomical context, using quantitative in situ hybridization chain reaction (qHCR) to perform accurate and precise relative quantitation of mRNA expression with subcellular resolution within whole-mount vertebrate embryos. Gene expression can be queried in two directions: read-out from anatomical space to expression space reveals co-expression relationships in selected regions of the specimen; conversely, read-in from multidimensional expression space to anatomical space reveals those anatomical locations in which selected gene co-expression relationships occur. As we demonstrate by examining gene circuits underlying somitogenesis, quantitative read-out and read-in analyses provide the strengths of flow cytometry expression analyses, but by preserving subcellular anatomical context, they enable bi-directional queries that open a new era for in situ hybridization. [ABSTRACT FROM AUTHOR]

All vertebrate embryos are exposed to maternally derived steroids during development. In placental vertebrates, metabolism of maternal steroids by the placenta modulates embryonic exposure, but how exposure is regulated in oviparous vertebrates is less clear. Recent work in oviparous vertebrates has demonstrated that steroids are not static molecules, as they can be converted to more polar steroid sulfates by sulfotransferase enzymes. Importantly, these steroid sulfates can be converted back to the parent compound by the enzyme steroid sulfatase (STS). We investigated when and where STS was present during embryonic development in the red-eared slider turtle, Trachemys scripta. We report that STS is present during all stages of development and in all tissues we examined. We conclude that STS activity may be particularly important for regulating maternal steroid exposure in oviparous vertebrates. [ABSTRACT FROM AUTHOR]

The neural crest is a transient structure in vertebrate embryos that produces migratory cells with an astonishing developmental potential. While neural crest fate maps have originally been established through interspecies transplantation assays, dye labeling, and retroviral infection, more recent methods rely on approaches involving transgenesis and genome editing. These technologies allowed the identification of minor neural crest-derived cell populations in tissues of non-neural crest origin. Furthermore, in vivo multipotency at the single cell level and stage-dependent fate acquisitions were demonstrated using genetic technologies. Finally, recent reports indicate that neural crest-derived cells become activated in response to injury to secrete factors supporting tissue repair. Thus, neural crest-derived cells apparently contribute to tissue formation and regeneration by cell autonomous and non-autonomous mechanisms. [ABSTRACT FROM AUTHOR]

Neural crest cells are multipotent progenitors that dynamically interpret diverse microenvironments to migrate significant distances as a loosely associated collective and contribute to many tissues in the developing vertebrate embryo. Uncovering details of neural crest migration has helped to inform a general understanding of collective cell migration, including that which occurs during cancer metastasis. Here, we discuss several commonalities and differences of neural crest and cancer cell migration and behavior. First, we focus on some of the molecular pathways required for the initial specification and potency of neural crest cells and the roles of many of these pathways in cancer progression. We also describe epithelial-to-mesenchymal transition, which plays a critical role in initiating both neural crest migration and cancer metastasis. Finally, we evaluate studies that demonstrate myriad forms of cell-cell and cell-environment communication during neural crest and cancer collective migration to highlight the remarkable similarities in their molecular and cell biological regulation. [ABSTRACT FROM AUTHOR]

Vertebrate embryonic patterning depends on signaling from Nodal, a TGFb superfamily member. There are three Nodal orthologs in zebrafish; southpaw directs left-right asymmetries, while squint and cyclops function earlier to pattern mesendoderm. TGFb member Vg1 is implicated in mesoderm formation but the role of the zebrafish ortholog, Growth differentiation factor 3 (Gdf3), has not been fully explored. We show that zygotic expression of gdf3 is dispensable for embryonic development, while maternally deposited gdf3 is required for mesendoderm formation and dorsal-ventral patterning. We further show that Gdf3 can affect left-right patterning at multiple stages, including proper development of regional cell morphology in Kupffer's vesicle and the establishment of southpaw expression in the lateral plate mesoderm. Collectively, our data indicate that gdf3 is critical for robust Nodal signaling at multiple stages in zebrafish embryonic development. [ABSTRACT FROM AUTHOR]

A decade ago, we believed that at least 300 RNA binding proteins (RBPs) were encoded in our genomes based on annotations of known or predicted RNA binding domains. Deciphering the roles of those RBPs in regulated gene expression was a vast frontier awaiting exploration. Since then, the field has developed a number of key tools that navigate the landscape of cellular RNA. These rely principally on UV crosslinking to create covalent bonds between RBPs and target RNAs in vivo , revealing not only target identities but also local binding sites upon RNA-Seq. More recently, a reverse protocol – mRNA interactome capture – has enabled the identification of the proteins that interact with mRNA. Astonishingly, the number of RBPs has grown to more than 1000, and we must now understand what they do. Here, we discuss the application of these methods to model organisms, focusing on the zebrafish Danio rerio , which provide unique biological contexts for the analysis of RBPs and their functions. [ABSTRACT FROM AUTHOR]

Despite the phenotypic divergence of early embryogenesis among vertebrates ( e.g. , the wide variety of cleavage and gastrulation patterns), all species converge into phenotypically similar mid-embryonic stages (particularly pharyngula embryos, which show the typical anatomical features of vertebrates, such as the pharyngeal arch), and evolutionary divergence occurs again thereafter. This observation coincides well with the recently supported developmental hourglass model; however, little is known about the nature of this conserved pharyngula period in vertebrates, and it is unclear why this mid-embryonic period has been conserved. By highlighting recent molecular-based studies, this review focuses on known information and what should be known on this topic, with a focus on vertebrate pharyngula embryos. [ABSTRACT FROM AUTHOR]

A constriction in the neural tube at the junction of the midbrain and hindbrain is a conserved feature of vertebrate embryos. The constriction is a defining feature of the midbrain-hindbrain boundary (MHB), a signaling center that patterns the adjacent midbrain and rostral hindbrain and forms at the junction of two gene expression domains in the early neural plate: an anterior otx2/wnt1 positive domain and a posterior gbx/fgf8 positive domain. otx2 and gbx genes encode mutually repressive transcription factors that create a lineage restriction boundary at their expression interface. Wnt and Fgf genes form a mutually dependent feedback system that maintains their expression domains on the otx2 or gbx side of the boundary, respectively. Constriction morphogenesis occurs after these conserved gene expression domains are established and while their mutual interactions maintain their expression pattern; consequently, mutant studies in zebrafish have led to the suggestion that constriction morphogenesis should be considered a unique phase of MHB development. We analyzed MHB morphogenesis in fgf8 loss of function zebrafish embryos using a reporter driven by the conserved wnt1 enhancer to visualize anterior boundary cells. We found that fgf8 loss of function results in a re-activation of wnt1 reporter expression posterior to the boundary simultaneous with an inactivation of the wnt1 reporter in the anterior boundary cells, and that these events correlate with relaxation of the boundary constriction. In consideration of other results that correlate the boundary constriction with Wnt and Fgf expression, we propose that the maintenance of an active Wnt-Fgf feedback loop is a key factor in driving the morphogenesis of the MHB constriction. [ABSTRACT FROM AUTHOR]

Knowledge of single-cell metabolism would provide a powerful look into cell activity changes as cells differentiate to all the tissues of the vertebrate embryo. However, single-cell mass spectrometry technologies have not yet been made compatible with complex three-dimensional changes and rapidly decreasing cell sizes during early development of the embryo. Here, we bridge this technological gap by integrating capillary microsampling, microscale metabolite extraction, and capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI-MS) to enable direct metabolic analysis of identified cells in the live frog embryo (Xenopus laevis). Microprobe CE-ESI-MS of <0.02% of the single-cell content allowed us to detect ~230 different molecular features (positive ion mode), including 70 known metabolites, in single dorsal and ventral cells in 8-to-32-cell embryos. Relative quantification followed by multivariate and statistical analysis of the data found that microsampling enhanced detection sensitivity compared to whole-cell dissection by minimizing chemical interferences and ion suppression effects from the culture media. In addition, higher glutathione/oxidized glutathione ratios suggested that microprobed cells exhibited significantly lower oxidative stress than those dissected from the embryo. Fast (5 s/cell) and scalable microsampling with minimal damage to cells in the 8-cell embryo enabled duplicate and triplicate metabolic analysis of the same cell, which surprisingly continued to divide to the 16-cell stage. Last, we used microprobe single-cell CE-ESI-MS to uncover previously unknown reorganization of the single-cell metabolome as the dorsal progenitor cell from the 8-cell embryo formed the neural tissue fated clone through divisions to the 32-cell embryo, peering, for the first time, into the formation of metabolic single-cell heterogeneity during early development of a vertebrate embryo. [ABSTRACT FROM AUTHOR]

Background: Despite the significance of chicken as a model organism, our understanding of the chicken transcriptome is limited compared to human. This issue is common to all non-human vertebrate annotations due to the difficulty in transcript identification from short read RNAseq data. While previous studies have used single molecule long read sequencing for transcript discovery, they did not perform RNA normalization and 5'-cap selection which may have resulted in lower transcriptome coverage and truncated transcript sequences. Results: We sequenced normalised chicken brain and embryo RNA libraries with Pacific Bioscience Iso-Seq. 5' cap selection was performed on the embryo library to provide methodological comparison. From these Iso-Seq sequencing projects, we have identified 60 k transcripts and 29 k genes within the chicken transcriptome. Of these, more than 20 k are novel lncRNA transcripts with ~3 k classified as sense exonic overlapping lncRNA, which is a class that is underrepresented in many vertebrate annotations. The relative proportion of alternative transcription events revealed striking similarities between the chicken and human transcriptomes while also providing explanations for previously observed genomic differences. Conclusions: Our results indicate that the chicken transcriptome is similar in complexity compared to human, and provide insights into other vertebrate biology. Our methodology demonstrates the potential of Iso-Seq sequencing to rapidly expand our knowledge of transcriptomics. [ABSTRACT FROM AUTHOR]

The Late Jurassic Lourinhã Formation is known for its abundant remains of dinosaurs, crocodylomorphs and other vertebrates. Among this record are nine localities that have produced either dinosaur embryos, eggs or eggshell fragments. Herein, we describe and identify the first crocodiloid morphotype eggs and eggshells from the Lourinhã Formation, from five occurrences. One clutch from Cambelas, composed of 13 eggs, eggshell fragments from Casal da Rola and Peralta, one crushed egg and eggshells from Paimogo North, and four crushed eggs as well as eggshell fragments from Paimogo South. We observed and confirmed diagnostic morphological characters for crocodiloid eggshells and which are consistent with a crocodylomorph affinity, such as the ellipsoidal shape, wedge-shaped shell units, triangular extinction under cross-polarized light, and tabular ultrastructure. This material is distinctive enough to propose two new ootaxa within the oofamily Krokolithidae, Suchoolithus portucalensis, oogen. and oosp. nov., for the material from Cambelas, the most complete clutch known for crocodiloid eggs, and Krokolithes dinophilus, oosp. nov., for the remaining material. These are the oldest crocodylomorph eggs known, extending the fossil record for this group to the Late Jurassic. Furthermore, except for the clutch from Cambelas, the material was found with theropod eggs and nests, in the other four occurrences, which seem to suggest some form of biological relationship, still unclear at this point. [ABSTRACT FROM AUTHOR]

During vertebrate embryonic development, early skin, muscle, and bone progenitor populations organize into segments known as somites. Defects in this conserved process of segmentation lead to skeletal and muscular deformities, such as congenital scoliosis, a curvature of the spine caused by vertebral defects. Environmental stresses such as hypoxia or heat shock produce segmentation defects, and significantly increase the penetrance and severity of vertebral defects in genetically susceptible individuals. Here we show that a brief exposure to a high osmolarity solution causes reproducible segmentation defects in developing zebrafish (Danio rerio) embryos. Both osmotic shock and heat shock produce border defects in a dose-dependent manner, with an increase in both frequency and severity of defects. We also show that osmotic treatment has a delayed effect on somite development, similar to that observed in heat shocked embryos. Our results establish osmotic shock as an alternate experimental model for stress, affecting segmentation in a manner comparable to other known environmental stressors. The similar effects of these two distinct environmental stressors support a model in which a variety of cellular stresses act through a related response pathway that leads to disturbances in the segmentation process. [ABSTRACT FROM AUTHOR]

Understanding how left-right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left-right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic 'left-right organizer'. These flows direct asymmetric activation of a conserved Nodal (TGFb) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left-right organizer, both of which are critical for effective cilia function during left-right patterning. Finally, using mosaic cell-labelling and timelapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left-right organizer. This suggests the possibility that these cells acquire left-right positional information prior to the appearance of cilia. [ABSTRACT FROM AUTHOR]

The chick embryonic eye is an excellent model for the study of vertebrate organogenesis. Key events in eye development involve thickening, invagination and cytodifferentiation of the lens primordium. While these events occur successively at different developmental stages, the extent to which these events are temporally related is largely unknown. Here we show that the lens invagination is highly sensitive to temperature. Lowering of incubation temperature to 29°C at embryonic day 2 delayed the onset of invagination of the lens, but not thickening and cytodifferentiation, leading to abnormal protrusion of the eye. The temperature shift also delayed the inward bending of the underlying retinal primordium, even in the absence of the lens. Taken together, our results suggest that lens invagination is initiated independently of thickening and cytodifferentiation, possibly by mechanisms associated with morphogenesis of the primordial retina. [ABSTRACT FROM AUTHOR]

We present a plausible account of the origin of the archetypal vertebrate bauplan . We offer a theoretical reconstruction of the geometrically regular structure of the blastula resulting from the sequential subdivision of the egg, followed by mechanical deformations of the blastula in subsequent stages of gastrulation. We suggest that the formation of the vertebrate bauplan during development, as well as fixation of its variants over the course of evolution, have been constrained and guided by global mechanical biases. Arguably, the role of such biases in directing morphology—though all but neglected in previous accounts of both development and macroevolution—is critical to any substantive explanation for the origin of the archetypal vertebrate bauplan . We surmise that the blastula inherently preserves the underlying geometry of the cuboidal array of eight cells produced by the first three cleavages that ultimately define the medial-lateral, dorsal-ventral, and anterior-posterior axes of the future body plan. Through graphical depictions, we demonstrate the formation of principal structures of the vertebrate body via mechanical deformation of predictable geometrical patterns during gastrulation. The descriptive rigor of our model is supported through comparisons with previous characterizations of the embryonic and adult vertebrate bauplane . Though speculative, the model addresses the poignant absence in the literature of any plausible account of the origin of vertebrate morphology. A robust solution to the problem of morphogenesis—currently an elusive goal—will only emerge from consideration of both top-down (e.g., the mechanical constraints and geometric properties considered here) and bottom-up (e.g., molecular and mechano-chemical) influences. [ABSTRACT FROM AUTHOR]

Transcription factors Runx1, CBFβ and GATA1/2/3 play essential roles in regulating hematopoietic development during embryogenesis of vertebrate. In previous study, the orthologous genes of Runt, CBFβ and GATA1/2/3 have been identified from scallop Chlamys farreri and proved to have conserved function in regulating hemocyte production. Here, these three transcription factors were selected as hematopoietic markers to explore potential developmental events of hematopoiesis during ontogenesis of scallop. The transcripts of Cf Runt, Cf CBFβ and Cf GATA were detected abundantly after 32-cell embryo, trochophore and morula stage, and reached to a peak level in 32-cell embryos and D-shaped veligers, pediveligers or gastrula respectively. Further whole-mount immunofluorescence assay showed that the immunoreactivity of Cf Runt was firstly observed at 32-cell stage and then its distribution was specialized gradually to the mesoderm during gastrulation. By trochophore, the expression of Cf Runt, Cf CBFβ and Cf GATA proteins occurred coincidently in two specific symmetry cell mass located bilaterally on prototroch, and then disappeared rapidly in D-shaped or umbonal vliger, respectively. However, remarkable expressions of the three transcription factors were observed consistently in a new sinus structure appeared at the dorsal anterior side of D-shaped and umbonal veliger. After bacterial challenge, the mRNA expression levels of the three transcription factors were up-regulated or down-regulated significantly in trochophore, D-shaped veliger and pediveliger, indicating the available hematopoietic regulation in scallop larvae. The results revealed that scallop might experience two waves of hematopoiesis during early development, which occurred in the bilateral symmetry cell mass of trochophore and the sinus structure of veliger. [ABSTRACT FROM AUTHOR]

Historically, egg-bound reptile embryos were thought to passively thermoconform to the nest environment. However, recent observations of thermal taxis by embryos of multiple reptile species have led to the widely discussed hypothesis that embryos behaviorally thermoregulate. Because temperature affects development, such thermoregulation could allow embryos to control their fate far more than historically assumed. We assessed the opportunity for embryos to behaviorally thermoregulate in nature by examining thermal gradients within natural nests and eggs of the common snapping turtle (Chelydra serpentina; which displays embryonic thermal taxis) and by simulating thermal gradients within nests across a range of nest depths, egg sizes, and soil types. We observed little spatial thermal variation within nests, and thermal gradients were poorly transferred to eggs. Furthermore, thermal gradients sufficiently large and constant for behavioral thermoregulation were not predicted to occur in our simulations. Gradients of biologically relevant magnitude have limited global occurrence and reverse direction twice daily when they do exist, which is substantially faster than embryos can shift position within the egg. Our results imply that reptile embryos will rarely, if ever, have the opportunity to behaviorally thermoregulate by moving within the egg. We suggest that embryonic thermal taxis instead represents a play behavior, which may be adaptive or selectively neutral, and results from the mechanisms for behavioral thermoregulation in free-living stages coming online prior to hatching. [ABSTRACT FROM AUTHOR]

During embryonic development, formation of individual vertebrae requires that the paraxial mesoderm becomes divided into regular segmental units known as somites. Somites are sequentially formed at the anterior end of the presomitic mesoderm ( PSM) resulting from functional interactions between the oscillatory activity of signals promoting segmentation and a moving wavefront of tissue competence to those signals, eventually generating a constant flow of new somites at regular intervals. According to the current model for somitogenesis, the wavefront results from the combined activity of two opposing functional gradients in the PSM involving the Fgf, Wnt and retinoic acid ( RA) signaling pathways. Here, I use published data to evaluate the wavefront model. A critical analysis of those studies seems to support a role for Wnt signaling, but raise doubts regarding the extent to which Fgf and RA signaling contribute to this process. [ABSTRACT FROM AUTHOR]

Gadiforms such as Atlantic haddock comprise some of the world's most economically important fisheries. Understanding the early life history of these fish is a prerequisite for predicting effects of a changing environment and increased human activities. Robust assessment of the effects of environmental impacts on the embryos of non-model vertebrates is hampered by a lack of molecular resources and detailed knowledge regarding the regulation of genes and pathways in early development. Here we used mRNA sequencing to link transcriptional changes to developmental processes in haddock, specifically, pattern formation and organogenesis. Temporal expression of key developmental genes was tightly anchored to either the appearance of visible structures or cellular processes characterised in model organisms. These findings demonstrate the high potential of developmental transcriptomics as an analytical tool for improved understanding of pathophysiological mechanisms leading to abnormal development in any vertebrate. [ABSTRACT FROM AUTHOR]

During vertebrate embryogenesis the interdigital mesenchyme is removed by programmed cell death (PCD), except in species with webbed limbs. Although bone morphogenetic proteins (BMPs) have long been known to be players in this process, it is unclear if they play a direct role in the interdigital mesenchyme or if they only act indirectly, by affecting fibroblast growth factor (FGF) signaling. A series of genetic studies have shown that BMPs act indirectly by regulating the withdrawal of FGF activity from the apical ectodermal ridge (AER); this FGF activity acts as a cell survival factor for the underlying mesenchyme. Other studies using exogenous factors to inhibit BMP activity in explanted mouse limbs suggest that BMPs do not act directly in the mesenchyme. To address the question of whether BMPs act directly, we used an interdigit-specific Cre line to inactivate several genes that encode components of the BMP signaling pathway, without perturbing the normal downregulation of AER-FGF activity. Of three Bmps expressed in the interdigital mesenchyme, Bmp7 is necessary for PCD, but Bmp2 and Bmp4 both have redundant roles, with Bmp2 being the more prominent player. Removing BMP signals to the interdigit by deleting the receptor gene, Bmpr1a , causes a loss of PCD and syndactyly, thereby unequivocally proving that BMPs are direct triggers of PCD in this tissue. We present a model in which two events must occur for normal interdigital PCD: the presence of a BMP death trigger and the absence of an FGF survival activity. We demonstrate that neither event is required for formation of the interdigital vasculature, which is necessary for PCD. However, both events converge on the production of reactive oxygen species that activate PCD. [ABSTRACT FROM AUTHOR]

In order to generate the tissues and organs of a multicellular organism, different cell types have to be generated during embryonic development. The first step in this process of cellular diversification is the formation of the three germ layers: ectoderm, endoderm and mesoderm. The ectoderm gives rise to the nervous system, epidermis and various neural crest-derived tissues, the endoderm goes on to form the gastrointestinal, respiratory and urinary systems as well as many endocrine glands, and the mesoderm will form the notochord, axial skeleton, cartilage, connective tissue, trunk muscles, kidneys and blood. Classic experiments in amphibian embryos revealed the tissue interactions involved in germ layer formation and provided the groundwork for the identification of secreted and intracellular factors involved in this process. We will begin this review by summarising the key findings of those studies. We will then evaluate them in the light of more recent genetic studies that helped clarify which of the previously identified factors are required for germ layer formation in vivo, and to what extent the mechanisms identified in amphibians are conserved across other vertebrate species. Collectively, these studies have started to reveal the gene regulatory network (GRN) underlying vertebrate germ layer specification and we will conclude our review by providing examples how our understanding of this GRN can be employed to differentiate stem cells in a targeted fashion for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Background Skeletal muscle fibers are multinucleated syncytia that arise from the fusion of mononucleated precursors, the myocytes, during embryonic development, muscle hypertrophy in post-embryonic growth and muscle regeneration after injury. Even though myocyte fusion is central to skeletal muscle differentiation, our current knowledge of the molecular mechanism of myocyte fusion in the vertebrates is rather limited. Previous work, from our group and others, has shown that the zebrafish embryo is a very useful model for investigating the cell biology and genetics of vertebrate myocyte fusion in vivo . Results Here, we report the generation of a stable transgenic zebrafish strain that expresses the Histone 2B-GFP (H2B-GFP) fusion protein in the nuclei of all fast-twitch muscle fibers under the control of the fast-twitch muscle-specific myosin light chain , phosphorylatable , fast skeletal muscle a ( mylpfa ) gene promoter. By introducing this transgene into a mutant for junctional adhesion molecule 3b ( jam3b ), which encodes a cell adhesion protein previously implicated in myocyte fusion, we demonstrate the feasibility of using this transgene for the analysis of myocyte fusion during the differentiation of the trunk musculature of the zebrafish embryo. Conclusions Since we know so little about the molecules regulating vertebrate myocyte fusion, we propose that the mylpfa : H2B-GFP transgene will be a very useful reporter for conducting forward and reverse genetic screens to identify new components regulating vertebrate myocyte fusion. [ABSTRACT FROM AUTHOR]

Cerberus is a key regulator of vertebrate embryogenesis. Its biological function has been studied extensively in frog and mouse embryos. Its ability to bind and antagonize the transforming growth factor-β (TGF-β) family ligand Nodal is well established. Strikingly, the molecular function of Cerberus remains poorly understood. The underlying reason is that Cerberus is a complex, multifunctional protein: It binds and inhibits multiple TGF-β family ligands, it may bind and inhibit some Wnt family members, and two different forms with distinct activities have been described. In addition, sequence homology between frog and mammalian Cerberus is low, suggesting that previous studies, which analyzed frog Cerberus function, may not accurately describe the function of mammalian Cerberus. We therefore undertook to determine the molecular activities of human Cerberus in TGF-β family signaling. Using purified proteins, surface plasmon resonance, and reporter gene assays, we discovered that human Cerberus bound and inhibited the TGF-β family ligands Activin B, BMP-6, and BMP-7, but not the frog Cerberus ligand BMP-2. Notably, full-length Cerberus successfully blocked ligand binding to type II receptors, but the short form was less effective. In addition, full-length Cerberus suppressed breast cancer cell migration but the short form did not. Thus, our findings expand the roles of Cerberus as TGF-β family signaling inhibitor, provide a molecular rationale for the function of the N-terminal region, and support the idea that Cerberus could have regulatory activities beyond direct inhibition of TGF-β family signaling. [ABSTRACT FROM AUTHOR]

Summary In vertebrate embryos, somites, the precursor of vertebrae, form from the presomitic mesoderm (PSM), which is composed of cells displaying signaling oscillations. Cellular oscillatory activity leads to periodic wave patterns in the PSM. Here, we address the origin of such complex wave patterns. We employed an in vitro randomization and real-time imaging strategy to probe for the ability of cells to generate order from disorder. We found that, after randomization, PSM cells self-organized into several miniature emergent PSM structures (ePSM). Our results show an ordered macroscopic spatial arrangement of ePSM with evidence of an intrinsic length scale. Furthermore, cells actively synchronize oscillations in a Notch-signaling-dependent manner, re-establishing wave-like patterns of gene activity. We demonstrate that PSM cells self-organize by tuning oscillation dynamics in response to surrounding cells, leading to collective synchronization with an average frequency. These findings reveal emergent properties within an ensemble of coupled genetic oscillators. [ABSTRACT FROM AUTHOR]

Summary We demonstrate the utility of the phytochrome system to rapidly and reversibly recruit proteins to specific subcellular regions within specific cells in a living vertebrate embryo. Light-induced heterodimerization using the phytochrome system has previously been used as a powerful tool to dissect signaling pathways for single cells in culture but has not previously been used to reversibly manipulate the precise subcellular location of proteins in multicellular organisms. Here we report the experimental conditions necessary to use this system to manipulate proteins in vivo. As proof of principle, we demonstrate that we can manipulate the localization of the apical polarity protein Pard3 with high temporal and spatial precision in both the neural tube and the embryo’s enveloping layer epithelium. Our optimizations of optogenetic component expression and chromophore purification and delivery should significantly lower the barrier for establishing this powerful optogenetic system in other multicellular organisms. [ABSTRACT FROM AUTHOR]

The amplification of distinct neural stem/progenitor cell subtypes during embryogenesis is essential for the intricate brain structures present in various vertebrate species. For example, in both mammals and birds, proliferative neuronal progenitors transiently appear on the basal side of the ventricular zone of the telencephalon (basal progenitors), where they contribute to the enlargement of the neocortex and its homologous structures. In placental mammals, this proliferative cell population can be subdivided into several groups that include Tbr2+ intermediate progenitors and basal radial glial cells (bRGs). Here,we report that basal progenitors in the developing avian palliumshow uniquemorphological andmolecular characteristics that resemble the characteristics of bRGs, a progenitor population that is abundant in gyrencephalic mammalian neocortex. Manipulation of LGN (Leu-Gly-Asn repeat-enriched protein) and Cdk4/cyclin D1, both essential regulators of neural progenitor dynamics, revealed that basal progenitors and Tbr2+ cells are distinct cell lineages in the developing avian telencephalon. Furthermore, we identified a small population of subapical mitotic cells in the developing brains of a wide variety of amniotes and amphibians. Our results suggest that unique progenitor subtypes are amplified in mammalian and avian lineages by modifying common mechanisms of neural stem/progenitor regulation during amniote brain evolution. [ABSTRACT FROM AUTHOR]

Thyroid hormone ( TH) is critical for vertebrate postembryonic development, a period around birth in mammals when plasma TH levels are high. Interestingly, TH receptors ( TRs), especially TRα, are expressed prior to the synthesis and secretion of zygotic TH, suggesting the existence of unliganded TR during development. However, the role of unliganded TR during mammalian development has been difficult to study, in part due to the relatively weak phenotype of TR knockout mice. Amphibian metamorphosis resembles postembryonic development in mammals and is controlled by TH via TRs. Like in mammals, TRα gene is highly activated and is the major TR expressed prior to the synthesis of endogenous TH. By using TALEN (transcriptional activator like effector nucleases)-mediated gene editing approach, we and others have now shown that unliganded TRα has two independent functions during Xenopus premetamorphosis, i.e. inhibiting growth rate and slowing development. Furthermore, molecular and transgenic studies have shown that unliganded TRα accomplishes these via the recruitment of histone deacetylase ( HDAC)-containing corepressor complexes to repress the expression of TH-inducible genes. [ABSTRACT FROM AUTHOR]

The somite is the most prominent metameric structure observed during vertebrate embryogenesis, and its metamerism preserves the characteristic structures of the vertebrae and muscles in the adult body. During vertebrate somitogenesis, sequential formation of epithelialized cell boundaries generates the somites. According to the 'clock and wavefront model,' the periodical and sequential generation of somites is achieved by the integration of spatiotemporal information provided by the segmentation clock and wavefront. In the anterior region of the presomitic mesoderm, which is the somite precursor, the orchestration between the segmentation clock and the wavefront achieves morphogenesis of somites through multiple processes such as determination of somite boundary position, generation of morophological boundary, and establishment of the rostrocaudal polarity within a somite. Recently, numerous studies using various model animals including mouse, zebrafish, and chick have gradually revealed the molecular aspect of the 'clock and wavefront' model and the molecular mechanism connecting the segmentation clock and the wavefront to the multiple processes of somite morphogenesis. In this review, we first summarize the current knowledge about the molecular mechanisms underlying the clock and the wavefront and then describe those of the three processes of somite morphogenesis. Especially, we will discuss the conservation and diversification in the molecular network of the somitigenesis among vertebrates, focusing on two typical model animals used for genetic analyses, i.e., the mouse and zebrafish. In this review, we described molecular mechanism for the generation of somites based on the spatiotemporal information provided by 'segmentation clock' and 'wavefront' focusing on the evidences obtained from mouse and zebrafish. [ABSTRACT FROM AUTHOR]

The zebrafish ( Danio rerio ) is frequently employed as model organism to explore vertebrate embryogenesis but little is known about the lipoxygenase pathway in this lower vertebrate. When we searched the zebrafish genome for lipoxygenase genes we detected seven different genes localized on four different chromosomes. Four of these genes ( ALOX2 , ALOX3a , ALOX3b , ALOX3c ) share a high degree of sequence conservation with the human ALOX5 gene, which encodes for the key enzyme of mammalian leukotriene biosynthesis. Expression profiles of the corresponding transcripts indicated that the ALOX2 gene is high level expressed during zebrafish embryogenesis whereas transcripts originating from the other three paralog genes could not be detected. To functionally compare human ALOX5 with the putative zebrafish ortholog (zebrafish ALOX2) we cloned and expressed the zebrafish enzyme in pro- and eukaryotic expression systems and characterized it as arachidonic acid 5S-lipoxygenating enzyme, which also exhibits leukotriene synthase activity. Mutagenesis studies of the triad determinants (Phe359Trp, Ala424Ile, Asn425Met) altered the reaction specificity from 5S- to dominant 15S-lipoxygenation. The finding that zebrafish expresses a functional ALOX5 together with the observation that most other human leukotriene relevant genes have an ortholog in the zebrafish genome suggests the biological relevance of leukotriene signaling in lower vertebrates. [ABSTRACT FROM AUTHOR]

Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways.We also identified members of the actin regulatoryWAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells' apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrateWAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems. [ABSTRACT FROM AUTHOR]

The innate immune system is the first line of defence against pathogens and infection. Recently, it has become apparent that many innate immune factors have roles outside of immunity and there is growing evidence that these factors play important functional roles during the development of a range of model organisms. Several studies have documented developmental expression of individual factors of the toll-like receptor and complement systems, and we recently demonstrated a key role for complement C5a receptor (C5aR1) signalling in neural tube closure in mice. Despite these emerging studies, a comprehensive expression analysis of these molecules in embryonic development is lacking. In the current study, we therefore, examined the expression of key innate immune factors in the early development period of neurulation (7.5–10.5 dpc) in mice. We found that complement factor genes were differentially expressed during this period of murine development. Interestingly, the expression patterns we identified preclude activation of the classical and alternative pathways and formation of the membrane attack complex. Additionally, several other classes of innate immune molecules were expressed during the period of neurulation, including toll-like receptors (TLR-2, -3, -4 and -9), receptor for advanced glycation end-products (RAGE), and their signalling adapters (TRAF-4, TRAF-6, TAK-1 and MyD88). Taken together, this study highlights a number of innate immune factors as potential novel players in early embryonic development. [ABSTRACT FROM AUTHOR]

Background Laterality in the vertebrate embryo is determined by left-right asymmetric gene expression driven by the flow of extraembryonic fluid across the embryonic node. Defects in these processes cause heterotaxy, the abnormal formation and arrangement of visceral organs that can range from complete inversion of symmetry to the selective misarrangement of organs. However, our understanding of the genetic causality for laterality defects in human beings remains relatively limited. Methods We performed whole exome sequencing in a consanguineous family with heterotaxia. To interrogate the pathogenic potential of the discovered variant, we used an in vivo system in which the potential of the candidate gene to induce L-R asymmetry was tested by transient suppression and CRISPR/Cas9-induced deletions. We also used in vitro assays to test a possible link between our exome-derived candidate and Notch signaling. Results We identified a homozygous 2 bp deletion in MMP21, encoding matrix metalloproteinase-21, as the sole coding mutation that segregated with the phenotype. Transient suppression or CRISPR/Cas9-mediated deletion of mmp21 in zebrafish embryos induced cardiac looping defects, with concomitant disruption of laterality markers in the lateral plate mesoderm and disrupted notch signalling in vitro and in vivo. Conclusions Our data implicate loss of MMP21 as a cause of heterotaxy in humans with concomitant defects in Notch signaling. In support of this finding, a homozygous missense mutation in MMP21 was identified previously in mice with N-Ethyl-N-Nitrosourea (ENU)- induced heterotaxy. Taken together, these observations suggest a role of matrix metalloproteinases in the establishment of asymmetric organ development, likely through the regulation of morphogenetic signals. [ABSTRACT FROM AUTHOR]

Summary A biochemical explanation of development from the fertilized egg to the adult requires an understanding of the proteins and RNAs expressed over time during embryogenesis. We present a comprehensive characterization of protein and mRNA dynamics across early development in Xenopus . Surprisingly, we find that most protein levels change little and duplicated genes are expressed similarly. While the correlation between protein and mRNA levels is poor, a mass action kinetics model parameterized using protein synthesis and degradation rates regresses protein dynamics to RNA dynamics, corrected for initial protein concentration. This study provides detailed data for absolute levels of ∼10,000 proteins and ∼28,000 transcripts via a convenient web portal, a rich resource for developmental biologists. It underscores the lasting impact of maternal dowry, finds surprisingly few cases where degradation alone drives a change in protein level, and highlights the importance of transcription in shaping the dynamics of the embryonic proteome. [ABSTRACT FROM AUTHOR]

In this review, we highlight recent re-evaluations of the classical cell sorting models and their application to understanding embryonic morphogenesis. Modern genetic and biophysical techniques reveal that tissue self-assembly is not solely a result of differential adhesion, but rather incorporates dynamic cytoskeletal tension and extracellular matrix assembly. There is growing evidence that these biomechanical modules cooperate to organize developing tissues. We describe the contributions of Cadherins and Integrins to tissue assembly and propose a model in which these very different adhesive regimes affect the same outcome through separate but convergent mechanisms. [ABSTRACT FROM AUTHOR]