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.
The brain and spinal cord begin as a tube that runs the length of the developing embryo. This tube made from cells called neural progenitors, which can divide to generate adult nerve cells. As nerve cells are born they detach from their neighbours, in a process called delamination before migrating away.
Though the delamination of nerve cells is important for the formation of the nervous system, scientists do not fully understand how proteins inside cells work together to release the newborn nerve cell from its neighbours. Two major components of the process are proteins called actin and tubulin, which form complex structures known as acto-myosin cables and microtubules respectively. Acto-myosin cables must contract during delamination, but the role of the microtubules is unclear.
Kasioulis et al. examined the microtubules in chick and mouse neural tube cells during delamination using fluorescent labels to mark key molecules and small molecule inhibitors to selectively block different activities. A combination of live tissue and super-resolution imaging were used to reveal the dynamics of the delamination process.
The experiments revealed a wheel-like configuration of microtubules that lined up with the acto-myosin cable. Actin maintained the microtubules, which in turn maintained the acto-myosin cable. As newborn neurons delaminated, the actin cable constricted and the microtubules condensed, forming a tunnel that allowed a structure that organises the microtubules – the centrosome – to move, and the cell to detach. A protein called Drebrin, which links actin to microtubules, was identified as a potential coordinator of the process.
These findings not only further our understanding of nervous system development, but may also shed light on the development of human diseases. Failure of delamination can lead to a spectrum of disorders, including epilepsy, dyslexia and intellectual disability. Cell detachment is also important in other developmental processes, as well as in the spread of cancer cells.