Biology subjects

Camacho de la Macorra, C.

Publications and source records attributed to Camacho de la Macorra, C..

4 recordsLinked to original sources

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↗

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↗

bioRxiv2020

Maternal vgll4a promotes blastoderm cohesion enabling yap1-mediated mechano-transduction during zebrafish epiboly

Cellular cohesion provides tissue tension, which is then sensed by the cytoskeleton and decoded by the activity of mechano-transducers, such as the transcriptional cofactor Yap1, thereby enabling morphogenetic responses in multi-cellular organisms. How cell cohesion is regulated is nevertheless unclear. Here we show that, zebrafish epiboly progression, a prototypic morphogenetic event that depends on Yap activity, requires the maternal contribution of the proposed yap1 competitor vgll4a. In embryos lacking maternal/zygotic vgll4a (MZvgll4a), spreading epithelial cells are ruffled, blastopore closure is delayed and the expression of the yap1-mediator arhgap18 is decreased, impairing the actomyosin ring at the syncytial layer. Furthermore, rather than competing with Yap1, vgll4a coordinate the levels of the E-Cadherin/{beta}-catenin adhesion complex components at the blastomere plasma membrane and hence their actin cortex distribution. Taking these results together, we propose that maternal vgll4a may act at epiboly initiation to coordinate blastomere adhesion/cohesion, which is a fundamental piece of the self-sustained bio-mechanical regulatory loop underlying morphogenetic rearrangements during gastrulation.

developmental biology↗