Biology subjects

Serrano Najera, G.

Publications and source records attributed to Serrano Najera, G..

7 recordsLinked to original sources

bioRxiv2026

Choreographed morphogenetic events underlie early foregut development in the mouse embryo

Between embryonic days 7.5 and 8.5, the mouse embryo undergoes a dramatic rearrangement of its entire anterior, a process known as ventral folding: the near-simultaneous morphogenesis of the cardiac crescent, cranial headfolds, and anterior foregut that together establish the antero-ventral body plan. While cardiac morphogenesis has been studied in detail, the cellular and mechanical basis of foregut involution remains largely undefined. Using combined light-sheet and spinning-disk live imaging spanning the full window of foregut formation, we show that involution proceeds through a stereotyped morphological programme that does not require actomyosin contractility for its initiation. Additionally, involution is preceded by a spatiotemporally restricted wave of apoptosis in embryonic visceral endoderm (emVE) cells, which extrude bidirectionally. A lineage- and stage-resolved bulk RNA-sequencing of emVE, definitive endoderm, and epiblast populations identifies a differential-adhesion and cell-cycle signature underlying this behaviour. Revisiting a visceral-endoderm-specific Bmp2 knock-out mutant, we find that BMP2 controls involution indirectly, by directing notochord positioning and thereby the geometry of the surrounding heart and headfold mechanics. Together, these findings reframe ventral folding as a single coordinated geometric process rather than a set of independent organ forming events.

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

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

Local optogenetic NMYII activation within the zebrafish neural rod results in long-range, asymmetric force propagation

How do cellular forces propagate through tissue to allow large-scale morphogenetic events? To investigate this question, we used an in vivo optogenetic approach to reversibly manipulate actomyosin contractility at depth within the developing zebrafish neural rod. Contractility was induced along the lateral cortices of a small patch of developing neural epithelial progenitor cells, resulting in a shortening of these cells along their mediolateral axis. Imaging the immediate response of surrounding tissue uncovered a long-range, tangential, and elastic tissue deformation along the anterior-posterior axis. Unexpectedly, this was highly asymmetric, propagating in either the anterior or the posterior direction in response to local gradients in optogenetic activation. The degree of epithelialisation did not have a significant impact on the extent of force propagation via lateral cortices. We also uncovered a dynamic oscillatory expansion and contraction of the tissue along the anterior-posterior axis, with wavelength within the range of rhombomere length. Together, this study shows dynamic and wave-like propagation of force along the anterior-posterior axis. It also suggests that cell generated forces are actively propagated over long distances within the tissue, and that local anisotropies in tissue organisation and contractility are sufficient to drive directional force propagation.

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↗

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↗