Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Cell Sci. 2010 Feb 1;123(Pt 3):484-96. doi: 10.1242/jcs.057851. Epub 2010 Jan 12.
During the development of the vertebrate nervous system, mitosis of neural progenitor cells takes place near the lumen, the apical side of the neural tube, through a characteristic movement of nuclei known as interkinetic nuclear migration (INM). Furthermore, during the proliferative period, neural progenitor cells exhibit planar cell divisions to produce equivalent daughter cells. Here, we examine the potential role of extracellular signals in INM and planar divisions using the medaka mutant tacobo (tab). This tab mutant shows pleiotropic phenotypes, including neurogenesis, and positional cloning identified tab as laminin gamma1 (lamc1), providing a unique framework to study the role of extracellular signals in neurogenesis. In tab mutant neural tubes, a number of nuclei exhibit abnormal patterns of migration leading to basally mislocalized mitosis. Furthermore, the orientation of cell division near the apical surface is randomized. Probably because of these defects, neurogenesis is accelerated in the tab neural tube. Detailed analyses demonstrate that extracellular signals mediated by the FAK pathway regulate INM and planar divisions in the neuroepithelium, possibly through interaction with the intracellular dynein-motor system.
在脊椎动物神经系统的发育过程中，神经祖细胞的有丝分裂发生在靠近腔室的地方，即神经管的顶端一侧，通过一种被称为核周迁移（INM）的核特征运动。此外，在增殖期，神经祖细胞通过平面细胞分裂产生相等的子细胞。在这里，我们使用斑马鱼突变体 tacobo（tab）研究细胞外信号在 INM 和平面分裂中的潜在作用。这个 tab 突变体表现出多种表型，包括神经发生，通过位置克隆确定 tab 为层粘连蛋白 γ1（lamc1），为研究细胞外信号在神经发生中的作用提供了独特的框架。在 tab 突变体神经管中，许多细胞核表现出异常的迁移模式，导致有丝分裂发生在基底部位。此外，靠近顶端表面的细胞分裂方向随机化。可能由于这些缺陷，tab 神经管中的神经发生加速。详细分析表明，FAK 途径介导的细胞外信号调节神经上皮中的 INM 和平面分裂，可能通过与细胞内的动力蛋白马达系统相互作用。
