Biology subjects

Bazellieres, E.

Publications and source records attributed to Bazellieres, E..

3 recordsLinked to original sources

bioRxiv2024

A multicellular actin star network underpins epithelial organization and connectivity

Epithelial tissues serve as physical barriers against various external pressures yet remarkably maintain structural stability. Various cellular apparatus including bicellular junction and actomyosin network contribute to the epithelial integrity, packing and remodelling. Although their role in morphogenetic and mechanical processes have been extensively studied during embryogenesis and disease development, their synergistic effects in maintaining tissue organization and connection remain poorly understood. In this study, we discovered a tissue-scale actomyosin network connected through bicellular junctions and manifested in the villi of adult murine intestinal tissue. Later we reproduced such supracellular structure in the differentiated compartment of ex vivo intestinal epithelium model. The self-organized actomyosin networks comprised individual actin nodes in each hexagonal cell at the epithelial base with six radial actin branches, presenting an actin star unit. The repeated units were connected through the bicellular junctions, forming a large, multicellular array covering the differentiated domains. Functionally, actin stars contribute to epithelial morphological stability by maintaining cell hexagonality and packing, thereby preserving the solid-like order of the epithelium. Laser ablation experiments validate a modified vertex theoretical model that connects the emergence of such solid-like order to the onset of tension along the actin star branches. Actin stars also acted as locks at the basal side minimizing protrusive activity in the epithelial layer, hindering cell migration and disorganization of the epithelial tissue. Altogether, the supracellular actin star network constitutes a basal biomechanical apparatus coordinating epithelial tissue stability and organization.

cell biology↗

bioRxiv2023

CRB3 and ARP2/3 regulate cell biomechanical properties to set epithelial monolayers for collective movement

Several cellular processes during morphogenesis, tissue healing or cancer progression involve epithelial to mesenchymal plasticity that leads to collective motion (plasticity?). Even though a rich variety of EMP programs exist, a major hallmark unifying them is the initial breaking of symmetry that modifies the epithelial phenotype and axis of polarity. During this process, the actin cytoskeleton and cellular junctions are extensively remodelled correlating with the build-up of mechanical forces. As the collective migration proceeds, mechanical forces generated by the actin cytoskeleton align with the direction of migration ensuring an organized and efficient collective cell behaviour, but how forces are regulated during the breaking of symmetry at the onset of EMP remains an unaddressed question. It is known that the polarity complex CRB3/PALS1/PATJ, and in particular, CRB3 regulates the organization of the actin cytoskeleton associated to the apical domain thus pointing at a potential role of CRB3 in controlling mechanical forces. Whether and how CRB3 influences epithelial biomechanics during the epithelial-mesenchymal plasticity remains, however, largely unexplored. Here, we systematically combine mechanical and molecular analyses to show that CRB3 regulates the biomechanical properties of collective epithelial cells during the initial breaking of symmetry of the EMP. CRB3 interacts with ARP2/3 and controls the remodelling of actin throughout the monolayer via the modulation of the Rho-/Rac-GTPase balance. Taken together, our results identified CRB3, a polarity protein, as a regulator of epithelial monolayer mechanics during EMP.

cell biology↗

bioRxiv2021

Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function

Ciliated epithelia perform a variety of essential functions across animal evolution, ranging from locomotion of marine organisms to mucociliary clearance of airways in mammals. These epithelia are composed of multiciliated cells (MCCs) harbouring myriads of motile cilia, which rest on modified centrioles called basal bodies (BBs), and beat coordinately to generate directed fluid flows. Thus, BB biogenesis and organization is central to MCC function. In basal eukaryotes, the coiled-coil domain proteins Lrrcc1 and Ccdc61 were shown to be required for proper BB construction and function. Here, we used the Xenopus embryonic ciliated epidermis to characterize Lrrcc1 and Ccdc61 in vertebrate MCCs. We found that they both encode BB components, with a prominent association to striated rootlets. Knocking down either gene caused defects in BB docking, spacing, and polarization. Moreover, their depletion impaired the apical cytoskeleton, and altered ciliary beating. Consequently, cilia-powered fluid flow was greatly reduced in morphant tadpoles, which displayed enhanced mortality when exposed to pathogenic bacteria. This work illustrates how integration across organizational scales make elementary BB components essential for the emergence of the physiological function of ciliated epithelia.

developmental biology↗