Biology subjects

Mayor, R.

Publications and source records attributed to Mayor, R..

7 recordsLinked to original sources

bioRxiv2026

Reciprocal mechanochemical feedback couples neural crest migration and neurulation

Cephalic neurulation and neural crest migration are defining morphogenetic events of vertebrate head development. Although traditionally viewed as independent tissue-autonomous programs, their striking spatiotemporal overlap suggests functional coupling. Here, we show that these processes are linked by reciprocal mechanochemical feedback. We find that collective neural crest migration is essential for neural tube closure. As neural crest cells delaminate and invade the surrounding mesoderm, they remodel fibronectin at the neural crest-neural plate interface, creating a specialized extracellular matrix that both separates the two tissues and promotes neural tube morphogenesis by enabling radial intercalation and apical constriction of neural plate cells. This extracellular matrix remodeling requires neural crest-specific expression of the membrane-bound metalloproteinase MMP14. Conversely, neural tube morphogenesis drives neural crest migration. Mechanical compression generated during neural plate bending induces MMP14 expression in neural crest cells, triggering extracellular matrix remodeling that feeds back to facilitate neural tube closure. Together, our findings reveal that neurulation and neural crest migration are not independent morphogenetic programs but components of a self-reinforcing mechanochemical circuit that coordinates vertebrate head morphogenesis.

developmental biology↗

bioRxiv2025

DySTrack: a modular smart microscopy tool for live tracking of dynamic samples on modern commercial microscopes

Advances in microscopy and bioimage analysis are enabling unprecedented quantitative observation of dynamic biological systems. Smart microscopy closes the loop by feeding back image-derived information to control image acquisition on the fly, paving the way for increasingly autonomous and sophisticated experiments. However, adoption of smart microscopy remains limited primarily to specialists, and even simple tasks such as live tracking of moving samples are still widely handled manually. Here we describe DySTrack, a modular open-source python tool that serves as a minimal bridge between commercial acquisition software and arbitrary image analysis pipelines, allowing users to stick with familiar vendor-developed user interfaces for microscope configuration whilst leveraging the powerful and platform-agnostic python ecosystem for image analysis. DySTrack comes with detailed documentation and with ready-to-use, easy-to-adapt example pipelines that track moving tissues (namely the zebrafish lateral line primordium and the chick Hensens node) during embryonic development. We hope DySTrack will contribute to a recent push to make smart microscopy more widely accessible.

developmental biology↗

bioRxiv2023

Gαi2-Mediated Regulation of Microtubules Dynamics and Rac1 Activity Orchestrates Cranial Neural Crest Cell Migration in Xenopus

Cell migration is a complex and essential process in various biological contexts, from embryonic development to tissue repair and cancer metastasis. Central to this process are the actin and tubulin cytoskeletons, which control cell morphology, polarity, focal adhesion dynamics, and overall motility in response to diverse chemical and mechanical cues. Despite the well-established involvement of heterotrimeric G proteins in cell migration, the precise underlying mechanism remains elusive, particularly in the context of development. This study explores the involvement of Gi2, a subunit of heterotrimeric G proteins, in cranial neural crest cell migration, a critical event in embryonic development. Our research uncovers the intricate mechanisms underlying Gi2 influence, revealing a direct interaction with the microtubule-associated protein EB1, and through this with tubulin, suggesting a regulatory function in microtubule dynamics modulation. Here, we show that Gi2 knockdown leads to microtubule stabilization, alterations in cell polarity and morphology with an increased Rac1-GTP concentration at the leading edge and cell-cell contacts, impaired cortical actin localization and focal adhesion disassembly. Interestingly, in Gi2 knockdown cells, RhoA-GTP was found to be reduced at cell-cell contacts and concentrated at the leading edge, providing evidence of Gi2 significant role in polarity. Remarkably, treatment with nocodazole, a microtubule-depolymerizing agent, effectively reduces Rac1 activity, restoring cranial NC cell morphology, actin distribution, and overall migration. Collectively, our findings shed light on the intricate molecular mechanisms underlying cranial neural crest cell migration and highlight the pivotal role of Gi2 in orchestrating microtubule dynamics through EB1 and EB3 interaction, modulating Rac1 activity during this crucial developmental process.

cell biology↗

bioRxiv2023

Frictiotaxis underlies adhesion-independent durotaxis

Cells move directionally along gradients of substrate stiffness, a process called durotaxis. The current consensus is that durotaxis relies on cell-substrate focal adhesions to sense stiffness and transmit forces that drive directed motion. Therefore, focal adhesion-independent durotaxis is thought to be impossible. Here, we show that confined cells can perform durotaxis despite lacking strong or specific adhesions. This durotactic migration depends on asymmetric myosin distribution and actomyosin retrograde flow. We show that the mechanism of this adhesion-independent durotaxis is that stiffer substrates offer higher friction. We propose a physical model that predicts that non-adherent cells polarise and migrate towards regions of higher friction - a process that we call frictiotaxis. We demonstrate frictiotaxis in experiments by showing that cells migrate up a friction gradient even when stiffness is uniform. Our results broaden the potential of durotaxis to guide any cell that contacts a substrate and reveal a new mode of directed migration based on friction, with implications for immune and cancer cells, which commonly move with non-specific interactions.

cell biology↗

bioRxiv2022

RanBP1 plays an essential role in directed migration of neural crest cells during development.

Collective cell migration is essential for embryonic development, tissue regeneration and repair, and has been implicated in pathological conditions such as cancer metastasis. It is, in part, directed by external cues that promote front-to-rear polarity in individual cells. However, our understanding of the pathways that underpin the directional movement of cells in response to external cues remains incomplete. To examine this issue we made use of neural crest cells (NC), which migrate as a collective during development to generate vital structures including bones and cartilage. Using a candidate approach, we found an essential role for Ran-binding protein 1 (RanBP1), a key effector of the nucleocytoplasmic transport pathway, in enabling directed migration of these cells. Our results indicate that RanBP1 is required for establishing front-to-rear polarity, so that NCs are able to chemotax. Moreover, our work suggests that RanBP1 function in chemotaxis involves the polarity kinase LKB1/PAR4. We envisage that regulated nuclear export of LKB1 through Ran/RanBP1 is a key regulatory step required for establishing front-to-rear polarity and thus chemotaxis, during NC collective migration.

developmental biology↗

bioRxiv2018

In vivo topology converts competition for cell-matrix adhesion into directional migration

When migrating in vivo, cells are exposed to numerous, and somewhat conflicting, signals: chemokines, repellents, extracellular matrix, growth factors. The roles of several of these molecules have been studied individually in vitro or in vivo but we have yet to understand how cells integrate them. To start addressing this question, we used the cephalic neural crest as a model system and looked at the roles of its best examples of positive and negative signals: stromal-cell derived factor 1 (Sdf1/Cxcl12) and class3-Semaphorins. Our results indicate that Sdf1 and Sema3A antagonistically control cell-matrix adhesion via opposite effects on Rac1 activity at the single cell level. Directional migration at the population level emerges as a result of global Semaphorin-dependent confinement and broad activation of adhesion by Sdf1 in the context of a biased Fibronectin distribution. These results indicate that uneven in vivo topology renders the need for precise distribution of secreted signals mostly dispensable.

developmental biology↗

bioRxiv2017

Connexin43 controls N-cadherin transcription during collective cell migration

Connexins are the primary components of gap junctions, providing direct links between cells in many physiological processes, including cell migration and cancer metastasis. Exactly how cell migration is controlled by gap junctions remains a mystery. To shed light on this, we investigated the role of Connexin43 in collective cell migration during embryo development using the neural crest, an embryonic cell population whose migratory behavior has been likened to cancer invasion. We discovered that Connexin43 is required for contact inhibition of locomotion by directly regulating the transcription of N-cadherin. For this function, the Connexin43 carboxy tail interacts with Basic Transcription Factor 3, which mediates its translocation to the nucleus. Together, they bind to the n-cad promotor regulating n-cad transcription. Thus, we uncover an unexpected, gap junction-independent role for Connexin43 in collective migration that illustrates the possibility that connexins, in general, may be important for a wide variety of cellular processes that we are only beginning to understand.\n\nHighlightsO_LICx43 regulates collective directional migration of neural crest cells\nC_LIO_LICx43 carboxy tail controls cell polarity via n-cad regulation\nC_LIO_LICx43 carboxy tail localises at the nucleus and that depends on BTF3\nC_LIO_LIBTF3 and Cx43 carboxy tail directly interact to bind and regulate n-cad promoter activity\nC_LI

developmental biology↗