Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Elife. 2017 Oct 23;6:e26215. doi: 10.7554/eLife.26215.
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.
新生儿神经元从神经上皮分离对于正确的神经元结构和功能回路是必需的。这个过程也称为分层，涉及黏着连接的解体和肌动球蛋白介导的断裂，在此过程中，中心体被保留，而顶/纤毛膜被丢弃。然而，介导分层的细胞生物学机制还知之甚少。使用活体组织和超分辨率成像，我们在鸡和鼠神经上皮细胞中发现了一种由中心体引发的轮状微管结构，与顶端肌动蛋白电缆和黏着连接对齐。这些微管在维持黏着连接的同时，肌动蛋白维持微管、黏着连接和顶端足的尺寸。在神经元分层过程中，肌球蛋白收缩产生一种隧道样的肌动蛋白微管结构，中心体通过该结构迁移。这种运动需要依赖肌动蛋白和微管的活性，我们确定 drebrin 是这些细胞骨架动力学的潜在协调蛋白。此外，中心体受损表明该细胞器对于分层是必需的。这些发现确定了新的细胞骨架结构和调节关系，这些关系协调神经元分层，并可能为上皮细胞病理性分离的机制提供信息。
