Biology subjects

Steventon, B.

Publications and source records attributed to Steventon, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Macroevolutionary shifts in post-hatching ontogeny and the origin of craniofacial disparity in fowl (Aves: Galloanserae)

Anseriformes (waterfowl) and Galliformes (landfowl) are among the worlds most recognisable groups of birds, together comprising the clade Galloanserae. Despite their close evolutionary relationship, the skulls of adult anseriforms and galliforms exhibit strikingly distinct morphologies, the developmental basis and evolutionary history of which is poorly understood. To illuminate the developmental and evolutionary underpinnings of cranial disparity between and within these major extant bird clades, we quantitatively investigated ontogenetic changes in cranial morphology across galloanseran phylogenetic diversity, focusing on the previously unexplored post-hatching interval during which adult morphology takes shape. Our results reveal the combined effects of multiple heterochronic shifts early in galloanseran evolutionary history including anseriform hypermorphosis, along with influential non-heterochronic changes leading to substantially more disparate ontogenetic trajectories--and greater cranial variability--in anseriforms than galliforms. Key galloanseran fossils help clarify the polarity of evolutionary shifts in cranial development through galloanseran phylogenetic history and demonstrate that extant galliform cranial morphology is more constrained and retains a more plesiomorphic morphology than that of anseriforms. Our work helps illuminate the developmental basis of the iconic differences in cranial form between waterfowl and landfowl and illustrates the importance of broad phylogenetic and ontogenetic sampling for clarifying patterns of post-hatching developmental divergence among major vertebrate clades.

evolutionary biology↗

bioRxiv2026

Dissecting planar and vertical organiser signals in early chick neural development.

Early neural development involves a combination of planar signals from the vertebrate organiser and vertical signals from its derived structures, the prechordal plate and notochord. However, the relative contribution of each structure to neural development is not clear. Here, we isolate anterior tissues from the primitive streak at successively later stages of development, to identify the extent of patterning that can occur prior to, during, and after the formation of the organiser and its later derivatives. Our results show that acquisition of neural identity occurs gradually and that exposure to planar signals from the developing node is necessary for neural plate specification. We also show that planar node-derived signals are required for AP patterning in isolated anterior tissues and give evidence that early neural tissue is of anterior character which subsequently becomes caudalised by signals (in part) from the developing node. However, anterior neural identity is lost without long-term contact with vertical signals from the axial mesendoderm. These results reveal a previously unappreciated level of autonomy in anterior neural development in the absence of node derived tissues. Summary statementCulture of isolated anterior tissues from the chick embryo reveal the roles of planar and vertical organiser signals for neural specification and anteroposterior patterning and maintenance.

developmental biology↗

bioRxiv2026

Long-Range Coupling of Posterior Cell Addition and Anterior Vacuolation Provides Robustness in Notochord Elongation.

Robust tissue growth control requires long-range communication between the rate of progenitor addition and tissue expansion. However, the regulatory mechanisms that couple these two processes are unknown. In zebrafish, notochord morphogenesis is a principal driver of axis extension through the combined actions of posterior progenitor addition and anterior vacuolation. To elucidate how progenitor dynamics and vacuole-driven cell expansion interact to shape notochord development, we first generated a mathematical model that links progenitor addition rate to the progressive expansion of cells from anterior-to-posterior to simulate vacuolation rate. Comparing this with empirical measurements, we find that progenitor incorporation together with vacuolation, produces a linear gradient in nearest neighbour distance. We next explored the role of YAP/TAZ in regulating the rate of progenitor addition in mutants for YAP/TAZ inhibitor vgll4b. We find that vgll4b expression and YAP activity are enriched in posterior midline progenitors. Loss of vgll4b elevates YAP signaling, enhances progenitor addition, restricts vacuole expansion, and--after a transient buffering phase--compromises A-P axis elongation. These results support a long-range feedback mechanism linking progenitor recruitment to vacuolation, enabling the notochord to balance cellular input with volumetric expansion, thereby maintaining tissue proportions. Graphical abstract. Proposed working model O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/706348v2_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@6c3c6dorg.highwire.dtl.DTLVardef@1f34eb0org.highwire.dtl.DTLVardef@b33a21org.highwire.dtl.DTLVardef@ad582b_HPS_FORMAT_FIGEXP M_FIG C_FIG A. Schematic representation of the authors proposed model illustrating how increased YAP activation in notochord progenitors of vgll4b mutants leads to enhanced progenitor addition to the notochord. This increased incorporation subsequently compromises the ability of notochord cells to undergo proper vacuolation, resulting in reduced axial elongation compared with control embryos.

developmental biology↗

bioRxiv2025

Reciprocal interactions between EMT and BMP signalling drive collective cell invasion.

During collective cell invasion, epithelial-to-mesenchymal transition (EMT) and morphogen signalling-mediated cell fate specification are traditionally viewed as a linear cascade: morphogens drive cell fates that activate EMT programs. Here, we uncover reciprocal coupling between EMT initiation and BMP signalling mediated by SNAI2 and SMAD1. Using substrate-induced EMT in ex vivo explants, we demonstrate that EMT initiation upregulates SMAD1 expression, priming cells for BMP signalling competence across germ layers. Single-cell RNA sequencing reveals SNAI2 and SMAD1 co-expression in EMT initiation regions, and SNAI2 overexpression is sufficient to induce ectopic SMAD1 expression in vivo. While BMP signalling is dispensable for EMT initiation, it regulates cell fate proportions, dispersal dynamics, precursor region depletion rates, and migration directionality. This coupling provides a mechanism for synchronising cell fate specification with invasion progression during axis elongation, positioning EMT as a process that actively modulates morphogen competence to coordinate tissue-level cell behaviours during collective cell invasion. HighlightsO_LIEMT initiation directly primes BMP pathway competence. C_LIO_LISNAI2 overexpression is sufficient to drive ectopic SMAD1 expression. C_LIO_LIBMP signalling is spatiotemporally restricted to EMT initiation zones. C_LIO_LIBMP signalling tunes cell fate proportions and invasion dynamics. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/691808v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@1ae1e78org.highwire.dtl.DTLVardef@526260org.highwire.dtl.DTLVardef@b892f1org.highwire.dtl.DTLVardef@1b74815_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2025

fgf8a signalling shapes brain divergence between Malawi cichlids

Brain diversification is intimately linked with adaptive radiations, yet the underlying molecular basis remains poorly understood. Here, we examine the mechanisms of neural evolution in two ecologically divergent Lake Malawi cichlid species: a generalist, Astatotilapia calliptera, and a pelagic piscivore, Rhamphochromis sp. chilingali. We demonstrate that forebrain domains diverged independently from other brain regions in these species, consistent with mosaic brain evolution. We identify fibroblast growth factor 8a (fgf8a) as a key factor underlying this neuroanatomical divergence. Species-specific fgf8a expression patterns during critical developmental windows correlate with adult brain differences. Functional knockout experiments confirm fgf8as essential role in cichlid brain patterning, directly linking this conserved developmental gene to interspecific neuroanatomical variation. We identify species-specific transposable element repertoires in the Malawi cichlid fgf8a locus that function as developmental enhancers in brain and sensory systems, providing a potential mechanism for expression divergence between species. Phylogenetic analysis across the radiation reveals elevated transposable element polymorphism at the fgf8a locus in Rhamphochromis, suggesting ongoing regulatory evolution in this clade. Our findings reveal how conserved developmental programmes can accommodate regulatory modification, providing a mechanistic framework for understanding rapid neural diversification during adaptive radiation.

developmental biology↗

bioRxiv2025

Gastruloids employ an alternative morphogenetic route to generate a posterior body axis on adherent substrates

Morphogenesis requires cells to integrate genetic and environmental information to pattern and shape tissues. Recent studies in vivo and in vitro have shown how alterations in environmental cues can induce alternative morphogenetic programs. However, what determines which morphogenetic strategy cells deploy in different environments remains unknown. Using gastruloids, a model for mammalian posterior body-axis elongation where environmental cues can be fully controlled in vitro, we show that substrate availability determines which force-generation strategy cells employ to build the body axis. In free-floating conditions, gastruloids self-assemble a single posterior body axis through cell-cell interactions. When plated on laminin, gastruloids acquire a flat morphology, break symmetry multiple times, and produce several independently elongating body axes through collective cell migration. On laminin, formin activity and focal adhesion-mediated traction are required for tissue elongation, yet both are functionally dispensable in free-floating conditions. Transcriptomic analysis shows that formin inhibition blocks elongation on laminin without any detectable transcriptional changes, demonstrating that these cytoskeletal components play a purely mechanical role that is only required when cells engage a substrate. Furthermore, laminin biases cells toward posterior migratory fates while preserving the Hox expression pattern. Together, these results show that mammalian body-axis elongation can proceed through different morphogenetic modes that engage distinct mechanical effectors depending on substrate availability. These findings have implications for understanding how evolution explores morphological diversity and how tissue engineering might achieve desired forms through precise environmental control.

developmental biology↗

bioRxiv2024

Live imaging human embryos reveals mitotic errors and lineage specification prior to implantation

Meiotic and mitotic chromosome segregation errors in human development have been studied mostly prior to and at the time of fertilisation. Despite chromosomal errors being a leading cause of miscarriage and infertility, chromosome missegregation has not been extensively studied at later stages of human development. Here we optimised labelling, light-sheet live imaging and semi-quantitative analysis of human embryos and reveal chromosome segregation errors just prior to implantation. We found that human embryos exhibited a number of chromosome missegregation events including multipolar spindle formation, lagging chromosomes, misalignment and chromosome slippage. We found that the majority of lagging chromosomes were passively inherited by one of the daughter cells, instead of reincorporating into the nuclei, suggesting a distinct pattern of micronuclei inheritance. By semi-automated segmentation, we tracked the position of labelled cells in human embryos and observed that while most labelled cells remained segregated to the outside, and therefore restricted to a placental-progenitor fate, there was evidence of a rare cell migration to cells positioned on the inside, which suggests that there may be plasticity. Altogether, we found that mitotic chromosome segregation errors arise just prior to implantation, which has implications for our understanding of biological events that contribute to aneuploidy mosaicism.

developmental biology↗

bioRxiv2024

Morphological criteria for staging near-hatching embryos of the domesticated Mallard (Anas platyrhynchos) and Swan Goose (Anser cygnoides)

Studying waterfowl embryology necessitates reliable and precise staging tables. These are descriptions of embryonic features throughout development from fertilisation to hatching stage, which are used to approximate the extent of embryonic development. Waterfowl staging tables have previously been established based on morphological features from fertilisation to approximately ten days before hatching. Embryonic changes over the final ten days of pre-hatching development have also been documented and proposed as useful staging criteria. However, the reliability of these changes as useful staging criteria across different waterfowl breeds has not been fully examined. To examine the reliability of these criteria-- which focus on size changes of the bill and middle toes--for staging near-hatching embryos, we examined twenty-seven Mallard and Swan Geese embryos and measured their beak and toe-length sizes. We compared our results with previously published data, and found that size variation across breeds within the same developmental stage is equivalent to within-breed variation across different stages, suggesting limited reliability of beak and middle toe length sizes for staging waterfowl embryos. Consequently, we devised novel staging criteria for waterfowl based on four easily measurable morphological traits and show that these criteria allow correct stage identification with over 70% accuracy. Our results highlight the importance of quantifying accuracy for developing reliable embryonic staging tables.

developmental biology↗

bioRxiv2024

Control of Modular Tissue Flows Shaping the Embryo in Avian Gastrulation

Avian gastrulation requires coordinated flows of thousands of cells to form the body plan. We quantified these flows using their fundamental kinematic units: one attractor and two repellers constituting its Dynamic Morphoskeleton (DM). We have also elucidated the mechanistic origin of the attractor, marking the primitive streak (PS), and controlled its shape, inducing gastrulation flows in the chick embryo that are typical of other vertebrates. However, the origins of repellers and dynamic embryo shape remain unclear. Here, we address these questions using active matter physics and experiments. Repeller 1, separating the embryo proper (EP) from extraembryonic (EE) tissues, arises from the tug-of-war between EE epiboly and EP isotropic myosin-induced active stress. Repeller 2, bisecting the anterior and posterior PS and associated with embryo shape change, arises from anisotropic myosin-induced active intercalation in the mesendoderm. Combining mechanical confinement with inhibition of mesendoderm induction, we eliminated either one or both repellers, as predicted by our model. Our results reveal a remarkable modularity of avian gastrulation flows delineated by the DM, uncovering the mechanistic roles of EE epiboly, EP active constriction, mesendoderm intercalation and ingression. These findings offer a new perspective for deconstructing morphogenetic flows, uncovering their modular origin, and aiding synthetic morphogenesis.

developmental biology↗

bioRxiv2024

Spinal Cord Elongation Enables Proportional Regulation of the Zebrafish Posterior Body

Early embryos display a remarkable ability to regulate the patterning of tissues in response to changes in tissue size. However, it is not clear whether this ability continues into post-gastrulation stages upon cell commitment to distinct germ layers. Here, we performed targeted removal of neural fated cells in the zebrafish tailbud using multi-photon ablation. This led to a proportional reduction in the length of both the spinal cord and paraxial mesoderm in the tail, revealing a capacity to regulate tissue morphogenesis across multiple tissues to build a well-proportioned posterior body. Following analysis of cell proliferation, gene expression, signalling and cell movements, we found no evidence of cell fate switching from mesoderm to neural fate to compensate for neural progenitor loss. Furthermore, we found that tail paraxial mesoderm length is not reduced upon direct removal of an equivalent number of mesoderm progenitors, ruling out the hypothesis that neuromesodermal competent cells enable proportional regulation. Instead, reduction in the numbers of cells across the spinal cord reduces both spinal cord and paraxial mesoderm length. We conclude that spinal cord elongation is a driver of paraxial mesoderm elongation in the zebrafish posterior body and that this can explain proportional regulation of both tissues upon neural progenitor reduction.

developmental biology↗

bioRxiv2023

Post-translational regulation of the Numb/Notch pathway in neurogenesis and cancer by Dlk2

Perturbations in fundamental developmental pathways have a profound influence on tumorigenesis. Numb plays a pivotal role in vertebrate development, including neurogenesis and is a key negative regulator of Notch signaling1, 2. Perturbation of Numb expression affects brain morphology and cell fate3. While extensive research has been conducted on canonical Notch ligands, regulation by vertebrate-specific non-canonical ligands is not understood. Here we identify Delta like non-canonical Notch ligand 2/EGFL9 (Dlk2) as a regulator of zebrafish neurogenesis with mutants exhibiting early increase and subsequent depletion of neural stem cells, decreased radial glial cells density, impaired neuronal cell distribution, and hypersensitivity to stimuli mimicking the embryonic murine Numb/Numblike null phenotype3. Numb function is inactivated by aberrant phosphorylation4, and we show that Dlk2 protein exhibits a high affinity direct interaction with Numb, with loss of Dlk2 in zebrafish telencephalon increasing Numb Ser276 phosphorylation with a concomitant increase in Notch signaling. Patients with tumors exhibiting reduced levels of Dlk2 have a poorer prognosis, while overexpression of Dlk2 in human cancer cell lines reduces cell proliferation. Our findings identify Dlk2 as a key partner of Numb, a gatekeeper of its activity, and an important player in a network of protein interactions regulating both neurogenesis and cancer with potential therapeutic implications.

cell biology↗

bioRxiv2023

Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids

Patterning and growth are fundamental features of embryonic development that must be tightly coordinated during morphogenesis. As metabolism can control cell growth while also providing mechanistic links to developmental signalling pathways, it is ideally placed to enable this coordination. To understand how metabolism impacts early mesoderm specification, we used mouse embryonic stem (ES) cell-derived gastruloids, as these enable temporal control over metabolic manipulations and can be generated in large quantities. Gastruloids show mosaic expression of two glucose transporters, Slc2a1 and Slc2a3 both of which co-express with the expression of both the mesodermal marker T/Bra and the neural marker Sox2. To understand the significance of cellular glucose uptake in development, we used the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG). 2-DG specifically blocks the expression of T/Bra without affecting the expression of Sox2 and abolishes axial elongation in gastruloids. Surprisingly, removing glucose completely from the medium did not phenocopy 2-DG treatment despite a significant decline in glycolytic intermediates occurring under both conditions. As 2-DG can also act as a competitive inhibitor of mannose, we added mannose together with 2-DG and found that it could rescue the mesoderm specification. Together, our results show that while mannose is crucial for mesoderm specification, the glycolytic pathway is dispensable at early stages of T/Bra expression in gastruloids.

developmental biology↗

bioRxiv2023

A population intrinsic timer controls Hox gene expression and cell dispersion during progenitor addition to the body axis

During embryonic development, the timing of events at the cellular level must be coordinated across multiple length scales to ensure the formation of a well-proportioned body plan. This is clear during somitogenesis, where the progenitors must be allocated to the axis over time whilst maintaining a progenitor population for continued elaboration of the body plan. However, the relative importance of intrinsic and extrinsic signals in timing progenitor addition at the single cell level is not yet understood. Heterochronic grafts from older to younger embryos have suggested a level of intrinsic timing whereby later staged cells contribute to more posterior portions of the axis. To determine the precise step at which cells are delayed, we performed single-cell transcriptomic analysis on heterochronic grafts of somite progenitors in the chicken embryo. This revealed a previously undescribed cell state within which heterochronic grafted cells are stalled, post-ingression through the primitive streak. The delayed exit of older cells from this state correlates with expression of posterior Hox genes. Using grafting and explant culture, we find that both Hox gene expression and the migratory capabilities of progenitor populations are intrinsically regulated at the population level. Therefore, we demonstrate that cell dispersion is controlled by a population intrinsic timer to control progenitor addition to the presomitic mesoderm.

developmental biology↗

bioRxiv2022

SARM1 detection in oligodendrocytes but not Schwann cells though sarm1/Sarm1 deletion does not perturb CNS nor PNS myelination in zebrafish and mice.

SARM1 is a central regulator of programmed axon death and is required to initiate axon self-destruction after traumatic and toxic insults to the nervous system. Abnormal activation of this axon degeneration pathway is increasingly recognized as a contributor to human neurological disease and SARM1 knockdown or inhibition has become an attractive therapeutic strategy to preserve axon loss in a variety of disorders of the peripheral and central nervous system. Despite this, it remains unknown whether Sarm1/SARM1 is present in myelinating glia and whether it plays a role in myelination in the PNS or CNS. It is important to answer these questions to understand whether future therapies inhibiting SARM1 function may have unintended deleterious impacts on myelination. Here we show that Sarm1 mRNA is present in oligodendrocytes in zebrafish but only detectable at low levels in Schwann cells in both zebrafish and mice. We find SARM1 protein is readily detectable in murine oligodendrocytes in vitro and in vivo and activation of endogenous SARM1 in oligodendrocytes induces cell death. In contrast, SARM1 protein is not detectable in Schwann cells and satellite glia in the adult murine nervous system. Cultured Schwann cells contain negligible functional SARM1 and are insensitive to specific SARM1 activators. Using zebrafish and mouse Sarm1 mutants, we show that SARM1 is not required for initiation of myelination nor myelin sheath maintenance by oligodendrocytes and Schwann cells. Thus, strategies to inhibit SARM1 function in the nervous system to treat neurological disease are unlikely to perturb myelination in humans. Main PointsO_LISARM1 protein is detectable in oligodendrocytes but not in Schwann cells C_LIO_LIOligodendrocytes but not Schwann cells die in response to endogenous SARM1 activation C_LIO_LICNS nor PNS myelination, in zebrafish and mice, is hindered by loss of sarm1/Sarm1 C_LI

neuroscience↗

bioRxiv2022

Zebrafish Neuromesodermal Progenitors Undergo a Critical State Transition in vivo

The transition state model of cell differentiation proposes that a transient window of gene expression stochasticity precedes entry into a differentiated state. As this has been assessed primarily in vitro, we sought to explore whether it can also be observed in vivo. Zebrafish neuromesodermal progenitors (NMps) differentiate into spinal cord and paraxial mesoderm at the late somitogenesis stages. We observed an increase in gene expression variability at the 24 somite stage (24ss) prior to their differentiation. From our analysis of a published 18ss scRNA-seq dataset, we showed that the NMp population possesses a signature consistent with a population undergoing a critical transition. By building in silico composite gene expression maps from our image data, we were able to assign an NM index to each in silico NMp based on the cumulative expression of its neural and mesodermal markers. With the NM index distributions, we demonstrated that cell population heterogeneity of the NMps peaked at 24ss. We then incorporated stochasticity and non-autonomy into a genetic toggle switch model and uncovered the existence of rebellious cells, which we then confirmed by reexamining the composite maps. Taken together, our work supports the transition state model within an endogenous cell fate decision making event.

developmental biology↗

bioRxiv2022

Approximated Gene Expression Trajectories (AGETs) for Gene Regulatory Network Inference on Cell Tracks

The study of pattern formation has greatly benefited from our ability to reverse-engineer gene regulatory network (GRN) structure from spatio-temporal quantitative gene expression data. Traditional approaches omit tissue morphogenesis, and focus on systems where the timescales of pattern formation and morphogenesis can be separated. In such systems, pattern forms as an emergent property of the underlying GRN and mechanistic insight can be obtained from the GRNs alone. However, this is not the case in most animal patterning systems, where patterning and morphogenesis are co-occurring and tightly linked. To address the mechanisms driving pattern formation in such systems we need to adapt our GRN inference methodologies to explicitly accommodate cell movements and tissue shape changes. In this work we present a novel framework to reverse-engineer GRNs underlying pattern formation in tissues undergoing morphogenetic changes and cell rearrangements. By integrating quantitative data from live and fixed embryos, we approximate gene expression trajectories (AGETs) in single cells and use a subset to reverse-engineer candidate GRNs using a Markov Chain Monte Carlo approach. GRN fit is assessed by simulating on cell tracks (live-modelling) and comparing the output to quantitative data-sets. This framework generates candidate GRNs that recapitulate pattern formation at the level of the tissue and the single cell. To our knowledge, this inference methodology is the first to integrate cell movements and gene expression data, making it possible to reverse-engineer GRNs patterning tissues undergoing morphogenetic changes.

systems biology↗

bioRxiv2021

The zebrafish presomitic mesoderm elongates through compression-extension

In vertebrate embryos the presomitic mesoderm become progressively segmented into somites at the anterior end while extending along the anterior-posterior axis. A commonly adopted model to explain how this tissue elongates is that of posterior growth, driven in part by the addition of new cells from uncommitted progenitor populations in the tailbud. However, in zebrafish, much of somitogenesis is associated with an absence of overall volume increase and posterior progenitors do not contribute new cells until the final stages of somitogenesis. Here, we perform a comprehensive 3D morphometric analysis of the paraxial mesoderm and reveal that extension is linked to a volumetric decrease, compression in both dorsal-ventral and medio-lateral axes, and an increase in cell density. We also find that individual cells decrease in their cell volume over successive somite stages. Live cell tracking confirms that much of this tissue deformation occurs within the presomitic mesoderm progenitor zone and is associated with non-directional rearrangement. Furthermore, unlike the trunk somites that are laid down during gastrulation, tail somites develop from a tissue that can continue to elongate in the absence of functional PCP signalling. Taken together, we propose a compression-extension mechanism of tissue elongation that highlights the need to better understand the role of tissue intrinsic and extrinsic forces play in regulating morphogenesis.

developmental biology↗

bioRxiv2021

Morphogenetic coupling leads to pattern emergence in the pre somitic mesoderm

As tissues elongate, cell rearrangement alters positional information in manner that must be accounted for to generate gene expression pattern. How this is achieved during paraxial mesoderm elongation is unknown. By reverse-engineering gene regulatory networks that predict single cell expression trajectories across the tissue, we find a network capable of recapitulating the full range of dynamic differentiation profiles observed both in vivo and in vitro. Simulating gene expression profiles on in toto cell tracking data sets reveal that temporal exposure to Wnt and FGF is generated by cell movement. The absence of reversal in gene expression towards a more premature gene expression state predicts the generation of aberrant tbx6 expression in the posterior progenitor zone that we then confirm by quantitative single cell imaging. Taken together, these results demonstrate cell rearrangement tunes the dynamics of mesoderm progenitor differentiation to generate pattern emergence as a function of temporal Wnt and FGF exposure.

developmental biology↗