Inter-dependent apical microtubule and actin dynamics orchestrate centrosome retention and neuronal delamination

Detachment of newborn neurons from the neuroepithelium is required for correct neuronal architecture and functional circuitry. This delamination process involves adherens junction disassembly and acto-myosin-mediated abscission, during which the centrosome is retained while apical/ciliary membrane 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.

Impact statement: Microtubules are nucleated by the centrosome of the primary cilium in the apical end-foot of neuroepithelial cells and interdependent microtubule and actin dynamics are required here to orchestrate delamination of newborn neurons.