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Results for “Developmental Biology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2016

Inhibition of cell proliferation does not slow down echinoderm neural regeneration

BackgroundRegeneration of the damaged central nervous system is one of the most interesting post-embryonic developmental phenomena. Two distinct cellular events have been implicated in supplying regenerative neurogenesis with cellular material - generation of new cells through cell proliferation and recruitment of already existing cells through cell migration. The relative contribution and importance of these two mechanisms is often unknown.\n\nMethodsHere, we use the regenerating radial nerve cord (RNC) of the echinoderm Holothuria glaberrima as a model of extensive post-traumatic neurogenesis in the deuterostome central nervous system. To uncouple the effects of cell proliferation from those of cell migration, we treated regenerating animals with aphidicolin, a specific inhibitor of S-phase DNA replication. Cell migration was tracked with vital staining with the lipophilic dye DiI.\n\nResultsAphidicolin treatment resulted in a significant 2.1-fold decrease in cell proliferation. In spite of this, the regenerating RNC in the treated animals did not differ in histological architecture, size and cell number from its counterpart in the control vehicle-treated animals. DiI labeling showed extensive cell migration in the RNC. Some cells migrated from as far as 2 mm away from the injury plane to contribute to the neural outgrowth.\n\nConclusionsWe suggest that inhibition of cell division in the regenerating RNC of H. glaberrima, is compensated for by recruitment of cells, which migrate into the RNC outgrowth from deeper regions of the neuroepithelium. Neural regeneration in echinoderms is thus a highly regulative developmental phenomenon, in which the size of the cell pool can be controlled either by cell proliferation or cell migration, and the latter can neutralize perturbations in the former.

Developmental Biology↗

bioRxiv2016

Different combinations of ErbB receptor dimers generate opposing signals that regulate cell proliferation in cardiac valve development

HB-EGF plays an indispensable role in suppression of cell proliferation in mouse valvulogenesis. However, ligands of the EGF receptor (EGFR/ErbB1), including HB-EGF, are generally considered as growth-promoting factors, as shown in cancers. HB-EGF binds to and activates ErbB1 and ErbB4. We investigated the role of ErbB receptors in valvulogenesis in vivo using ErbB1- and ErbB4-deficient mice, and an ex vivo model of endocardial cushion explants. We show that HB-EGF suppresses valve mesenchymal cell proliferation through a heterodimer of ErbB1 and ErbB4, and an ErbB1 ligand(s) promotes cell proliferation through a homodimer of ErbB1. Moreover, a rescue experiment with cleavable or uncleavable isoforms of ErbB4 in ERBB4 null cells suggests that the cytoplasmic intracellular domain of ErbB4, rather than the membrane-anchored tyrosine kinase, achieves this suppression. Our study demonstrates that opposing signals generated by different ErbB dimer combinations function in the same cardiac cushion mesenchymal cells for proper cardiac valve formation.\n\nSummary statementIn valvulogenesis, opposing signals generated by different combinations of ErbB-dimers elaborately regulate cell proliferation, in which proteolytically released intracellular domain of ErbB4 activated by HB-EGF is required to suppress proliferation.

Developmental Biology↗

bioRxiv2016

A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila

Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. In Tribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels in Drosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition, and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects.\n\nAuthor summaryDifferent insect species exhibit one of two distinct modes of determining their body segments during development: they either use a molecular oscillator to position segments sequentially, or they generate segments simultaneously through a hierarchical gene-regulatory cascade. The sequential mode is ancestral, while the simultaneous mode has been derived from it independently several times during evolution. In this paper, we present evidence which suggests that simultaneous segmentation also involves an oscillator in the posterior of the embryo of the vinegar fly, Drosophila melanogaster. This surprising result indicates that both modes of segment determination are much more similar than previously thought. Such similarity provides an important step towards explaining the frequent evolutionary transitions between sequential and simultaneous segmentation.

Developmental Biology↗

bioRxiv2016

Conserved traits of spiralian development in the bryozoan Membranipora membranacea

BackgroundSpiral cleavage is a remarkably conserved pattern of embryogenesis present in animals of the clade Spiralia, such as annelids, molluscs, flatworms and nemerteans. However, not all spiralians display spiral cleavage. Recent phylogenies suggest that the spiral arrangement of embryonic blastomeres is an ancestral trait for the Spiralia and that it was secondarily modified in several spiralian lineages, such as gastrotrichs, brachiopods and bryozoans. To better understand the evolution of cleavage patterns in relation to blastomere fate maps and embryonic gene expression, we describe the cell lineage and molecular patterning in the embryogenesis of the bryozoan Membranipora membranacea.\n\nResultsM. membranacea develops through a unique stereotypic cleavage pattern with biradial symmetry and an embryo organized in identical quadrants with synchronous cell divisions. The quadrant identities are established as early as the 28-cell stage, when one vegetal blastomere (3D) activates the MAPK pathway, marking the future posterior region of the larva. Cells from this posterior quadrant divide asynchronously in subsequent stages leading to the morphological differentiation between quadrants. The first quartet of M. membranacea gives rise to the apical organ and ciliated band, the second and third quartet forms the oral/anal ectoderm, the fourth quartet the mesoderm and the vegetal blastomeres form the endoderm. We found that the early embryonic organization and the fate map of these early blastomeres in the bryozoan embryo are similar to a typical spiral-cleaving embryo. Furthermore we observe that correspondent blastomeres between the bryozoan and spiral-cleaving embryos share similar molecular identities, as revealed by the activity of MAPK and the expression of otx and foxa. The development of M. membranacea mainly differs from spiral-cleaving embryos in the downstream portions of the cell lineage, and in the origin of the mesoderm, which is formed by multiple fourth quartet blastomeres.\n\nConclusionsThe similarity between the fate map of M. membranacea and spiral-cleaving embryos indicates that the cleavage geometry of the bryozoan evolved decoupled from other spiralian developmental traits. In this case, the blastomere fates remained evolutionarily conserved despite the drastic modification in the cleavage pattern from spiral to biradial. These findings suggest that blastomere fates of spiral-cleaving embryos might not be linked to the stereotypic spiral cleavage pattern, but depend on other factors, such as the underlying molecular patterning. Our comparative analysis on the bryozoan reveals yet another facet of how early development evolves and helps to shed some light into the developmental diversity of spiralians.

Developmental Biology↗

bioRxiv2016

Evo-engineering and the Cellular and Molecular Origins of the Vertebrate Spinal Cord

The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specify spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posterior localized signalling source transforms previously anterior-specified neural plate into the spinal cord. In the second, a population of bipotent stem cells undergo continuous self-renewal and differentiation to progressively lay down the spinal cord and axial mesoderm by posterior growth. Whether this represents fundamental differences between the experimental model organisms utilised in the generation of these models remains to be addressed. Here we review lineage studies across four key vertebrate models: mouse, chicken, Xenopus and zebrafish and relate this to the underlying gene regulatory networks that are known to be required for spinal cord formation. We propose that by applying a dynamical systems approach to understanding how distinct neural and mesodermal fates arise from a bipotent progenitor pool, it is possible to begin to understand how differences in the dynamical cell behaviours such as proliferation rates and cell movements can map onto conserved regulatory networks to generate diversity in the timing of tissue generation and patterning during development.

Developmental Biology↗

bioRxiv2016

Eph/ephrin signaling controls progenitor identities in the ventral spinal cord

SUMMARY STATEMENTThis article by Laussu et al. describes a role for Eph:ephrin signaling in controlling the identity of neural progenitors in the ventral spinal cord.\n\nEarly specification of progenitors of the ventral spinal cord involves the morphogen Sonic Hedgehog which induces distinct progenitor identities in a dose-dependent manner. Following these initial patterning events, progenitor identities have to be maintained in order to generate appropriate numbers of progeny. Here we provide evidence that communication via Eph:ephrin signaling is required to maintain progenitor identities in the ventral spinal cord. We show that ephrinB2 and ephrinB3 are expressed in restricted progenitor domains in the ventral spinal cord while several Eph receptors are more broadly expressed. Further, we provide evidence that expression of Efnb3 and EphA4 is controlled by Shh. Genetic loss-of-function analyses indicate that expression of ephrinB2 and ephrinB3 is required to control progenitor identities and in vitro experiments reveal that activation of Eph forward signaling in spinal progenitors up-regulates the expression of the identity transcription factor Nkx2.2. Altogether our results indicate that cell-to-cell communication is necessary to control progenitor identity in the ventral spinal cord.

Developmental Biology↗

bioRxiv2016

Cholesterol activates the G-protein coupled receptor Smoothened to promote morphogenetic signaling

Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike most GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown to mediate cholesterol binding to the CRD in a recent structural analysis also dictate SMO activation, both in response to cholesterol and to native Hh ligands. Our results show that cholesterol can initiate signaling from the cell surface by engaging the extracellular domain of a GPCR and suggest that SMO activity may be regulated by local changes in cholesterol abundance or accessibility.

Developmental Biology↗

bioRxiv2016

PAPC couples the Segmentation Clock to somite morphogenesis by regulating N-cadherin dependent adhesion

Vertebrate segmentation is characterized by the periodic formation of epithelial somites from the mesenchymal presomitic mesoderm (PSM). How the rhythmic signaling pulse delivered by the Segmentation Clock is translated into the periodic morphogenesis of somites remains poorly understood. Here, we focused on the role of Paraxial protocadherin (PAPC/Pcdh8) in this process. We show that in chicken and mouse embryos, PAPC expression is tightly regulated by the Clock and Wavefront system in the posterior PSM. We observed that PAPC exhibits a striking complementary pattern to N-Cadherin (CDH2), marking the interface of the future somite boundary in the anterior PSM. Gain and loss of function of PAPC in chicken embryos disrupt somite segmentation by altering the CDH2-dependent epithelialization of PSM cells. Our data suggest that clathrin-mediated endocytosis is increased in PAPC expressing cells, subsequently affecting CDH2 internalization in the anterior compartment of the future somite. This in turn generates a differential adhesion interface, allowing formation of the acellular fissure that defines the somite boundary. Thus periodic expression of PAPC downstream of the Segmentation Clock triggers rhythmic endocytosis of CDH2, allowing for segmental de-adhesion and individualization of somites.

Developmental Biology↗

bioRxiv2016

TAF10 is required for the integrity of TFIID and SAGA complexes but is initially dispensable for somitogenesis in the mouse embryo

Cell fate and patterning during development are controlled by gene expression. Pre-initiation complex (PIC) formation at promoters is crucial to recruit the transcriptional machinery. The PIC has mainly been studied in vitro, and little is known about its composition and function during development. TAF10 is a subunit of TFIID and of the transcriptional co-activator SAGA. Here we characterized TFIID and SAGA's composition during mouse development. Our data indicate that TAF10 is required for TFIID and SAGA assembly. To analyse TAF10-dependent gene regulation during development, we conditionally deleted Taf10 in the mesoderm. Our results provide evidence for a time window during which Taf10 loss in the presomitic mesoderm (PSM) does not prevent cyclic gene transcription or PSM patterning while lateral plate differentiation is profoundly altered. During this period, global steady state mRNA levels are not significantly affected in the PSM although the expression of a subset of specific genes is dysregulated. Together, our data demonstrate a differential sensibility of mesodermal tissues to the lack of TAF10. This supports a differential requirement for TAF10 by the general transcriptional machinery during different developmental processes.

Developmental Biology↗

bioRxiv2016

Hand2 Inhibits Kidney Specification While Promoting Vein Formation Within the Posterior Mesoderm

Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidneyby restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.\n\nIMPACT STATEMENTThe Hand2 transcription factor regulates the dimensions of the kidney by controlling cell fate decisions at the interface between organ fields.

Developmental Biology↗

bioRxiv2016

Geometry can provide long-range mechanical guidance for embryogenesis

Downstream of gene expression, effectors such as the actomyosin contractile machinery drive embryo morphogenesis. During Drosophila embryonic axis extension, actomyosin has a specific planar-polarised organisation, which is responsible for oriented cell intercalation. In addition to these cell rearrangements, cell shape changes also contribute to tissue deformation. While cell-autonomous dynamics are well described, understanding the tissue-scale behaviour challenges us to solve the corresponding mechanical problem at the scale of the whole embryo, since mechanical resistance of all neighbouring epithelia will feedback on individual cells. Here we propose a novel numerical approach to compute the whole-embryo dynamics of the actomyosin-rich apical epithelial surface. We input in the model specific patterns of actomyosin contractility, such as the planar-polarisation of actomyosin in defined ventro-lateral regions of the embryo. Tissue strain rates and displacements are then predicted over the whole embryo surface according to the global balance of stresses and the material behaviour of the epithelium. Epithelia are modelled using a rheological law that relates the rate of deformation to the local stresses and actomyosin anisotropic contractility. Predicted flow patterns are consistent with the cell flows observed when imaging Drosophila axis extension in toto, using light sheet microscopy. The agreement between model and experimental data indicates that the anisotropic contractility of planar-polarised actomyosin in the ventro-lateral germband tissue can directly cause the tissue-scale deformations of the whole embryo. The three-dimensional mechanical balance is dependent on the geometry of the embryo, whose curved surface is taken into account in the simulations. Importantly, we find that to reproduce experimental flows, the model requires the presence of the cephalic furrow, a fold located anteriorly of the extending tissues. The presence of this geometric feature, through the global mechanical balance, guides the flow and orients extension towards the posterior end.\n\nAuthor SummaryThe morphogenesis of living organisms is a facinating process during which a genetic programme controls a sequence of molecular changes which will cause the original embryo to acquire a new shape. While we have a growing knowledge of the timing and spatial distribution of key molecules downstream of genetic programmes, there remain gaps of understanding on how these patterns can generate the appropriate mechanical force, so as to deform the tissues in the correct manner. In this paper, we show how a model of tissue mechanics can link the known pattern of actomyosin distribution in Drosophila tissues to the process of axis extension, which is a ubiquitous morphogenetic movement of developing animal embryos. We show in numerical simulations that the correct movement is obtained only if the geometry of the embryo presents some precise features. This means that prior morphogenetic movements responsible for these features need to have succeeded in order to carry on the next round of morphogenesis. This highlights the contribution of mechanical feedback on the morphogenetic programme and also how mechanical action integrates at the scale of the whole embryo.

Developmental Biology↗

bioRxiv2016

PDGF signaling directs cardiomyocyte movement toward the midline during heart tube assembly

Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. In both zebrafish and mouse, mutation of pdgfra inhibits cardiac fusion and can lead to cardia bifida. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline. Intriguingly, the ligand pdgfaa is expressed in the endoderm medial to the pdgfra-expressing myocardial precursors. Ectopic expression of pdgfaa interferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication guides the cell movements that initiate cardiac morphogenesis.\n\nIMPACT STATEMENTStudies in zebrafish and mouse implicate the PDGF signaling pathway in the communication between the endoderm and the myocardium that drives medial myocardial movement and thereby initiates cardiac morphogenesis.

Developmental Biology↗

bioRxiv2016

PCR artifact in testing for homologous recombination in genomic editing in zebrafish

We report a PCR-induced artifact in testing for homologous recombination in zebrafish. We attempted to replace the lnx2a gene with a donor cassette, mediated by a TALEN induced double stranded cut. The donor construct was flanked with homology arms of about 1 kb at the 5 and 3 ends. Injected embryos (G0) were raised and outcrossed to wild type fish. A fraction of the progeny appeared to have undergone the desired homologous recombination, as tested by PCR using primer pairs extending from genomic DNA outside the homology region to a site within the donor cassette. However, Southern blots revealed that no recombination had taken place. We conclude that recombination happened during PCR in vitro between the donor integrated elsewhere in the genome and the lnx2a locus, as suggested by earlier work [1]. We conclude that PCR alone may be insufficient to verify homologous recombination in genome editing experiments in zebrafish.

Developmental Biology↗

bioRxiv2016

A Novel function for Cactus/IκB inhibitor to promote Toll signals in the Drosophila embryo

The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila embryo Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the I{kappa}B inhibitor Cactus resulting in a nuclear gradient of the NF{kappa}B effector Dorsal. Here we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and Dorsal target genes. Quantitative analysis using a series of loss and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient behave differently respective to Cactus fluctuations. Unexpectedly, Cactus favors Dorsal nuclear localization required as response to high Toll signals at the ventral side of the embryo. Furthermore, N-terminal deleted Cactus mimics these effects, indicating that the ability of Cactus to favor Toll stems from mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that unexplored mechanisms are at play to ensure a correct response to high Toll signals.\n\nSummaryThe I{kappa}B protein Cactus favors high Toll signals, revealing that the ventral and lateral aspects of the Dorsal/NF{kappa}B nuclear gradient behave differently respective to Cactus concentrations in the Drosophila embryo.

Developmental Biology↗

bioRxiv2016

A shielded irradiation assay to investigate mechanisms of in vivo stem cell migration in planarians

Migration of stem cells underpins the physiology of metazoan animals. For tissues to be maintained, stem cells and their progeny must migrate and differentiate in the correct positions. This need is even more acute after tissue damage by wounding or pathogenic infections. Inappropriate migration also underpins the formation of metastasis. Despite this, few mechanistic studies address stem cell migration during repair or homeostasis in adult tissues. Here, we present a shielded X-ray irradiation assay that allows us to follow stem cell migration in the planarians. We demonstrate that we can use this system to study the molecular control of stem cell migration and show that snail and zeb-1 EMT transcription factors homologs are necessary for cell migration to wound sites and for the establishment of migratory cell morphology. Our work establishes planarians as a suitable model for further in depth study of the processes controlling stem cell migration in vivo.

developmental biology↗

bioRxiv2016

A regulated environment for micro-organs defines essential conditions for intercellular Ca2+ waves

The mechanical stress state of an organ is a critical, but still poorly understood, driver of organogenesis and regeneration. Here we report a chip-based regulated environment for micro-organs (REM-Chip) that enables systematic investigations of the crosstalk between an organs mechanical stress environment and biochemical signaling under a multitude of genetic and chemical perturbations. This method has enabled us to identify essential conditions for generating organ-scale intercellular calcium (Ca2+) waves (ICWs) in Drosophila wing imaginal discs that are also observed in vivo. Spontaneous ICWs require the presence of components in fly extract-based growth serum (FEX). Using the REM-Chip, we demonstrate that the release and not the initial application of mechanical compression is sufficient but not necessary to initiate ICWs. Further, the extent of the Ca2+ response is heterogeneous between discs and correlates with the degree of spontaneous ICWs activity in the pre-stress state. This system and method enable detailed examinations of the interplay between mechanical stress state, biochemical regulatory networks, and physiology in complex, hierarchically organized organ cultures.

developmental biology↗

bioRxiv2016

Chimeric Genes Revealed in the Polyploidy Fish Hybrids of Carassius cuvieri (Female) x Megalobrama amblycephala (Male)

The genomes of newly formed natural or artificial polyploids may experience rapid gene loss and genome restructuring. In this study, we obtained tetraploid hybrids (4n=148, 4nJB) and triploid hybrids (3n=124, 3nJB) derived from the hybridization of two different subfamily species Carassius cuvieri ([female], 2n = 100, JCC) and Megalobrama amblycephala ([male], 2n = 48, BSB). Some significant morphological and physiological differences were detected in the polyploidy hybrids compared with their parents. To reveal the molecular traits of the polyploids, we compared the liver transcriptomes of 4nJB, 3nJB and their parents. The results indicated high proportion chimeric genes (31 > %) and mutated orthologous genes (17 > %) both in 4nJB and 3nJB. We classified 10 gene patterns within three categories in 4nJB and 3nJB orthologous gene, and characterized 30 randomly chosen genes using genomic DNA to confirm the chimera or mutant. Moreover, we mapped chimeric genes involved pathways and discussed that the phenotypic novelty of the hybrids may relate to some chimeric genes. For example, we found there is an intragenic insertion in the K+ channel kcnk5b, which may be related to the novel presence of the barbels in 4nJB. Our results indicated that the genomes of newly formed polyploids experienced rapid restructuring post-polyploidization, which may results in the phenotypic and phenotypic changes among the polyploidy hybrid offspring. The formation of the 4nJB and 3nJB provided new insights into the genotypic and phenotypic diversity of hybrid fish resulting from distant hybridization between subfamilies.

developmental biology↗

bioRxiv2016

Collective epithelial migration drives timely morphogenesis of the retinal neuroepithelium

Organ formation is a multi-scale event that involves changes at the intracellular, cellular and tissue level. Organogenesis often starts with the formation of characteristically shaped organ precursors. However, the cellular mechanisms driving organ precursor formation are often not clear. Here, using zebrafish, we investigate the epithelial rearrangements responsible for the development of the hemispherical retinal neuroepithelium (RNE), a part of the optic cup. We show that in addition to basal shrinkage of RNE cells, active migration of connected epithelial cells into the RNE is a crucial player in its formation. This cellular movement is driven by progressive cell-matrix contacts and actively translocates prospective RNE cells to their correct location before they adopt neuroepithelial fate. Failure of this migration during neuroepithelium formation leads to ectopic determination of RNE cells and consequently impairs optic cup formation. Overall, this study illustrates how spatiotemporal coordination between morphogenic movements and fate determination critically influences organogenesis.

developmental biology↗