Biology subjects

Taberner, N.

Publications and source records attributed to Taberner, N..

4 recordsLinked to original sources

bioRxiv2024

Circumferential actomyosin bundles drive endothelial cell deformations to constrict blood vessels

Following the formation of new blood vessels, vascular remodelling ensues to generate a hierarchical network of vascular tubes with optimal connections and diameters for efficient blood perfusion of tissues. How transitions in endothelial cell (EC) number and shape are coordinated to define vessel diameter during development remains an open question. In this study, we discovered EC deformations, rearrangements and transient formation of self-seam junctions as key mechanisms that explain a negative relationship between cell number and vessel diameter. High-resolution analysis of actin cytoskeleton organization disclosed the generation of tension-bearing, circumferential actomyosin bundles in the endothelial cortex that drive EC deformation and vessel constriction. Importantly, the loss of circumferential actin bundles in krit1/ccm1-deficient ECs causes cell enlargement and impaired vessel constriction that culminate in dilated vessels, characteristic of cerebral cavernous malformation. Our multiscale study therefore underpins circumferential actomyosin-driven EC deformations in controlling vessel size and in the prevention of vascular malformations.

cell biology↗

bioRxiv2021

Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues

During embryonic development, cellular forces synchronize in space and time to generate functional tissue shapes. Apical constriction is one of these force-generating processes, and it is necessary to modulate epithelial curvature in fundamental morphogenetic events, such as neural tube folding. The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution of each cellular process to complex morphogenesis. However, the shortage of tools to manipulate three-dimensional (3D) shapes of mammalian tissues currently hinders the progress of the field. Here we report the development of "OptoShroom3", a new optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. Activation of OptoShroom3 through illumination of individual cells in an epithelial cell sheet reduced their apical surface while illumination of groups of cells caused deformation in the adjacent regions. By using OptoShroom3, we further manipulated 3D tissue shapes. Light-induced apical constriction provoked the folding of epithelial cell colonies on soft gels. Its application to murine and human neural organoids led to thickening of neuroepithelia, apical lumen reduction in optic vesicles, and flattening in neuroectodermal tissues. These results show that spatiotemporal control of apical constriction can trigger several types of 3D deformation depending on the initial tissue context.

developmental biology↗

bioRxiv2020

Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size

The formation of vascular tubes is driven by extensive changes in endothelial cell (EC) shape. Here, we have identified a novel role of the actin-binding protein, Marcksl1, in modulating the mechanical properties of EC cortex to regulate cell shape and vessel structure during angiogenesis. Increasing and depleting Marcksl1 expression level in vivo resulted in an increase and decrease, respectively, in EC size and the diameter of microvessels. Furthermore, endothelial overexpression of Marcksl1 induced ectopic blebbing on both apical and basal membranes, during and after lumen formation, that is suppressed by reduced blood flow. High resolution imaging revealed that Marcksl1 promotes the formation of linear actin bundles and decreases actin density at the EC cortex. Our findings demonstrate that a balanced network of linear and branched actin at the EC cortex is essential in conferring cortical integrity to resist the deforming forces of blood flow to regulate vessel structure.

cell biology↗

bioRxiv2019

Motor-mediated clustering at microtubule plus ends facilitates protein transfer to a bio-mimetic cortex

Polarized protein distributions at the cortex play an important role in the spatial organization of cells. In S. pombe, growing microtubule ends contribute to the establishment and maintenance of such distributions by delivering specific factors to membrane receptors at the poles of the cell. It is however unclear how microtubule plus-end tracking of proteins favours protein accumulation at the cell cortex compared to proteins arriving directly from the cytoplasm. To address this question, we developed an in vitro assay, where microtubules were made to deliver His-tagged plus-end tracking proteins to functionalized microchamber walls. We found that motor-mediated protein clusters formed at microtubule ends were able to transfer to the walls, but non-clustered proteins were not. We further show that this transfer mechanism leads to preferential cluster accumulation at chamber poles, when microtubules are confined to elongated microfabricated chambers with sizes and shapes similar to S. pombe.

cell biology↗