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Vermot, J.

Publications and source records attributed to Vermot, J..

8 recordsLinked to original sources
bioRxiv2026

Viscosity-mediated signal amplification enables robust left-right symmetry breaking in the mouse node

Left-right (LR) symmetry breaking in vertebrates depends on a directional fluid flow generated in the embryonic LR organizer, yet how this flow is sensed remains unresolved. Mechanosensing and chemosensing models each capture part of the process but face key limitations when considered independently. Here, we introduce a minimal theoretical model of viscosity-mediated signal amplification that unifies these perspectives. In this framework, macromolecules secreted by organizer cells locally increase the near-surface viscosity, creating another viscous fluid layer that is entrained by the leftward nodal flow. This layer can significantly amplifies the drag and torque exerted on immotile perinodal cilia, enabling robust discrimination of flow direction even when flow magnitudes on the left and right are nearly identical. The model naturally incorporates macromolecule secretion, clarifies the complementary roles of motile and immotile cilia, and resolves the major shortcomings of previous proposals. Together, these results provide a simple and physically grounded mechanism for LR determination in the mouse node.

biophysics↗
bioRxiv2021

Extracellular mechanical forces drive endocardial cell volume decrease during cardiac valve morphogenesis

Organ morphogenesis involves dynamic changes of tissue properties at the cellular scale. In addition, cells need to adapt to their mechanical environment through mechanosensitive pathways. How mechanical cues influence cell behaviors during morphogenesis, however, remains poorly understood. Here we studied the influence of mechanical forces during the formation of the atrioventricular canal (AVC) where cardiac valves develop. We show that in zebrafish the AVC forms within a zone of tissue convergence between the atrium and the ventricle which is associated with increased activation of the actomyosin meshwork and endocardial cell orientation changes. We demonstrate that tissue convergence occurs with a major reduction of endocardial cell volume triggered by mechanical forces and the mechanosensitive channels TRPP2/TRPV4. In addition, we show that the extracellular matrix component hyaluronic acid controls cell volume changes. Together, our data suggest that cell volume change is a key cellular feature activated by mechanical forces during cardiovascular morphogenesis. This work further unravels how mechanical forces and extracellular matrix can influence tissue remodeling in developing organs.

developmental biology↗
bioRxiv2019

How to define and optimize axial resolution in light-sheet microscopy: a simulation-based approach

\"How thick is your light sheet?\" is a question that has been asked frequently after talks showing impressive renderings of 3D data acquired by a light-sheet microscope. This question is motivated by the fact that most of the time the thickness of the light-sheet is uniquely associated to the axial resolution of the microscope. However, the link between light-sheet thickness and axial resolution has never been systematically assessed and it is still unclear how both are connected. The question is not trivial because commonly employed measures cannot readily be applied or do not lead to easily interpretable results for the many different types of light sheet. Here, by using simulation data we introduce a set of intuitive measures that helps to define the relationship between light sheet thickness and axial resolution. Unexpectedly, our analysis revealed a trade-off between better axial resolution and thinner light-sheet thickness. Our results are surprising because thicker light-sheets that provide lower image contrast have previously not been associated with better axial resolution. We conclude that classical Gaussian illumination beams should be used when image contrast is most important, and more advanced types of illumination represent a way to optimize axial resolution at the expense of image contrast.

biophysics↗
bioRxiv2019

Intraflagellar transport complex B proteins regulate the Hippo effector Yap1 during cardiogenesis

Cilia and the intraflagellar transport (IFT) proteins involved in ciliogenesis are associated with congenital heart diseases (CHD). However, the molecular links between cilia, IFT proteins and cardiogenesis are yet to be established. Using a combination of biochemistry, genetics, and live imaging methods, we show that IFT complex B proteins (Ift88, Ift54 and Ift20) modulate the Hippo pathway effector YAP1 in zebrafish and mouse. We demonstrate that this interaction is key to restrict the formation of the proepicardium and the myocardium. In cellulo experiments suggest that IFT88 and IFT20 interact with YAP1 in the cytoplasm and functionally modulates its activity, identifying a molecular link between cilia related proteins and the Hippo pathway. Taken together, our results highlight a novel role for IFT complex B proteins during cardiogenesis and shed light on an unexpected mechanism of action for ciliary proteins in YAP1 regulation. These findings provide mechanistic insights into a non-canonical role for cilia related proteins during cardiogenesis.

developmental biology↗
bioRxiv2019

Rere-dependent Retinoic Acid signaling controls brain asymmetry and handedness

While the vertebrate brain appears largely bilaterally symmetrical in humans, it presents local morphological Left-Right (LR) asymmetries as, for instance, in the petalia. Moreover, higher functions such as speech or handedness are asymmetrically localized in the cortex. How these brain asymmetries are generated remains unknown. Here, we reveal a striking parallel between the control of bilateral symmetry in the brain and in the precursors of vertebrae called somites, where a \"default\" asymmetry is buffered by Retinoic Acid (RA) signaling. This mechanism is evident in zebrafish and mouse and, when perturbed in both species, it translates in the brain into lateralized alterations of patterning, neuronal differentiation and behavior. We demonstrate that altering levels of the mouse RA coactivator Rere results in subtle cortex asymmetry and profoundly altered handedness, linking patterning and function in the motor cortex. Together our data uncover a novel mechanism that could underlie the establishment of brain asymmetries and handedness in vertebrates.

neuroscience↗
bioRxiv2019

Mechanically activated Piezo channels control outflow tract valve development through Yap1 and Klf2-Notch signaling axis

Mechanical forces are well known for modulating heart valve developmental programs. Yet, it is still unclear how genetic programs and mechanosensation interact during heart valve development. Here, we assessed the mechanosensitive pathways involved during zebrafish outflow tract (OFT) valve development in vivo. Our results show that the hippo effector Yap1, Klf2, and the Notch signaling pathway are all essential for OFT valve morphogenesis in response to mechanical forces, albeit active in different cell layers. Furthermore, we show that Piezo and TRP mechanosensitive channels are essential for regulating these pathways. In addition, live reporters reveal that piezo controls Klf2 and Notch activity in the endothelium and Yap1 expression in the smooth muscle progenitors to coordinate OFT valve morphogenesis. Together, this work identifies a unique morphogenetic program during OFT valve formation and places Piezo as a central modulator of the cell response to forces in this process.

developmental biology↗
bioRxiv2018

Chiral cilia orientation in the left-right organizer

Chirality is a property of asymmetry between an object and its mirror image. Most biomolecules and cells are intrinsically chiral. Whether cellular chirality can be transferred to asymmetry at the tissue scale remains an unresolved issue. This question is particularly relevant in the left-right organizer (LRO), where cilia motility and chiral flow are thought to be the main drivers of left-right axis symmetry breaking. Here, we built a quantitative approach based on live imaging to set apart the contributions of various pathways to the spatial orientation of cilia in the Kupffers vesicle (KV, zebrafish LRO). We found that cilia populating the zebrafish LRO display an asymmetric orientation between the right and left side of the LRO. Cilia orientations, therefore, give the KV cells a sense of chirality which is different from the chirality of cilia rotation. Surprisingly, we found this asymmetry does not depend on the left-right signalling pathway or flow. Furthermore, we show the establishment of the chirality is dynamic and depends on planar cell polarity. Together, this work identifies a different type of asymmetry in the LRO and sheds light on the complexity of chirality genesis in developing tissues.

developmental biology↗