Del Bene Filippo, Wehman Ann M, Link Brian A, Baier Herwig
Department of Physiology, Programs in Neuroscience, Genetics, and Developmental Biology, University of California San Francisco, San Francisco, CA 94158-2722, USA.
Cell. 2008 Sep 19;134(6):1055-65. doi: 10.1016/j.cell.2008.07.017.
The different cell types in the central nervous system develop from a common pool of progenitor cells. The nuclei of progenitors move between the apical and basal surfaces of the neuroepithelium in phase with their cell cycle, a process termed interkinetic nuclear migration (INM). In the retina of zebrafish mikre oko (mok) mutants, in which the motor protein Dynactin-1 is disrupted, interkinetic nuclei migrate more rapidly and deeply to the basal side and more slowly to the apical side. We found that Notch signaling is predominantly activated on the apical side in both mutants and wild-type. Mutant progenitors are, thus, less exposed to Notch and exit the cell cycle prematurely. This leads to an overproduction of early-born retinal ganglion cells (RGCs) at the expense of later-born interneurons and glia. Our data indicate that the function of INM is to balance the exposure of progenitor nuclei to neurogenic versus proliferative signals.
中枢神经系统中的不同细胞类型由共同的祖细胞池发育而来。祖细胞的细胞核在细胞周期的相应阶段在神经上皮的顶端和基底表面之间移动，这一过程称为动核迁移（INM）。在斑马鱼mikre oko（mok）突变体的视网膜中，动力蛋白动力蛋白-1被破坏，动核向基底侧迁移得更快、更深，向顶端侧迁移得更慢。我们发现，Notch信号在突变体和野生型的顶端侧均主要被激活。因此，突变体祖细胞较少暴露于Notch，从而过早退出细胞周期。这导致早期生成的视网膜神经节细胞（RGC）过度产生，而后期生成的中间神经元和神经胶质细胞则减少。我们的数据表明，INM的功能是平衡祖细胞核暴露于神经源性信号与增殖信号的程度。
