Abstract
Detachment of newborn neurons from the neuroepithelium is required for correct neuronal architecture and functional circuitry. This process, also known as delamination, involves adherens-junction disassembly and acto-myosin-mediated abscission, during which the centrosome is retained while apical/ciliary membranes are shed. Cell-biological mechanisms mediating delamination are, however, poorly understood. Using live-tissue and super-resolution imaging, we uncover a centrosome-nucleated wheel-like microtubule configuration, aligned with the apical actin cable and adherens-junctions within chick and mouse neuroepithelial cells. These microtubules maintain adherens-junctions while actin maintains microtubules, adherens-junctions and apical end-foot dimensions. During neuronal delamination, acto-myosin constriction generates a tunnel-like actin-microtubule configuration through which the centrosome translocates. This movement requires inter-dependent actin and microtubule activity, and we identify drebrin as a potential coordinator of these cytoskeletal dynamics. Furthermore, centrosome compromise revealed that this organelle is required for delamination. These findings identify new cytoskeletal configurations and regulatory relationships that orchestrate neuronal delamination and may inform mechanisms underlying pathological epithelial cell detachment.
Highlights
Delamination involves extraction of a cell from within a proliferative tissue
We uncover a conserved wheel-like microtubule organisation, composed of rim and radial microtubules nucleated by the centrosome, which spans the apical end-foot and aligns with the actin cable and linked AJs
We show that apical actin maintains these microtubules, which are in turn required for maintenance of AJs and that apical actin serves to define end-foot dimensions
Summary
Delamination involves extraction of a cell from within a proliferative tissue. It is a fundamental process underlying epithelial tissue morphogenesis that is linked to cell state change during normal differentiation and to cancer cell dispersal. A genetic basis for human periventricular heterotopia has been mapped to the actin cross-linking protein, FilaminA and the ADP-ribosylation factor guanine exchange factor 2 ARFGEF2/BIG2 (Lian and Sheen, 2015) The interaction between these proteins has implicated them in vesicle trafficking and stability/turnover of cell adhesion proteins (Zhang et al, 2013; Zhang et al, 2012). Experiments in animal models implicate further regulators of cell adhesion in neuronal delamination, including Slit/Robo, which acts by attenuating N-cadherin activity (Wilsch-Brauninger et al, 2016; Wong et al, 2012) (Borrell et al, 2012) Overall, many such proteins associated with apically localised adherens
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