Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
J Cell Sci. 2022 Mar 15;135(6). doi: 10.1242/jcs.259897. Epub 2022 Mar 30.
Dynamic contacts between cells within the developing neuroepithelium are poorly understood but play important roles in cell and tissue morphology and cell signalling. Here, using live-cell imaging and electron microscopy we reveal multiple protrusive structures in neuroepithelial apical endfeet of the chick embryonic spinal cord, including sub-apical protrusions that extend laterally within the tissue, and observe similar structures in human neuroepithelium. We characterise the dynamics, shape and cytoskeleton of these lateral protrusions and distinguish them from cytonemes, filopodia and tunnelling nanotubes. We demonstrate that lateral protrusions form a latticework of membrane contacts between non-adjacent cells, depend on actin but not microtubule dynamics, and provide a lamellipodial-like platform for further extending fine actin-dependent filipodia. We find that lateral protrusions depend on the actin-binding protein WAVE1 (also known as WASF1): misexpression of mutant WAVE1 attenuated protrusion and generated a round-ended apical endfoot morphology. However, this did not alter apico-basal cell polarity or tissue integrity. During normal neuronal delamination, lateral protrusions were withdrawn, but precocious protrusion loss induced by mutant WAVE1 was insufficient to trigger neurogenesis. This study uncovers a new form of cell-cell contact within the developing neuroepithelium, regulation of which prefigures neuronal delamination. This article has an associated First Person interview with the first author of the paper.
神经上皮细胞之间的动态接触知之甚少，但在细胞和组织形态以及细胞信号转导中发挥着重要作用。在这里，我们使用活细胞成像和电子显微镜技术，揭示了鸡胚脊髓神经上皮细胞的顶侧足突中存在多种突起结构，包括在组织内横向延伸的亚顶突，并且在人类神经上皮中也观察到了类似的结构。我们描述了这些侧突的动力学、形状和细胞骨架，并将其与纤毛、丝状伪足和管状纳米通道区分开来。我们证明了侧突在非相邻细胞之间形成了细胞膜接触的晶格结构，依赖于肌动蛋白但不依赖于微管动力学，并为进一步延伸精细的肌动蛋白依赖的丝状伪足提供了类似于片状伪足的平台。我们发现侧突依赖于肌动蛋白结合蛋白 WAVE1（也称为 WASF1）：突变型 WAVE1 的异常表达减弱了突起的形成，并产生了圆形的顶侧足突形态。然而，这并没有改变顶底细胞极性或组织完整性。在正常的神经元分层过程中，侧突会回缩，但突变型 WAVE1 引起的过早回缩不足以触发神经发生。本研究揭示了发育中的神经上皮细胞内的一种新的细胞-细胞接触形式，其调节预示着神经元的分层。本文附有该论文第一作者的第一人称采访。
