LoTurco Joseph J, Sarkisian Mathew R, Cosker Laurie, Bai Jilin
Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269-4156, USA.
Cereb Cortex. 2003 Jun;13(6):588-91. doi: 10.1093/cercor/13.6.588.
Successful cell division in neural progenitors in the neocortical ventricular zone (VZ), as in all dividing cells, depends critically upon coordinating chromosome segregation during mitosis with cytokinesis. This coordination further suggests that common molecular regulators may link events in mitosis with those in cytokinesis. Recent genetic evidence indicates that cytokinesis in CNS neuronal progenitors, but not in most other cell types of the body, requires the function of citron kinase. In neocortex, citron kinase is most critical for neurogenic cytokinesis. In citron kinase null mutants, a large proportion of neuronal cells within neocortex are binucleate; however, very few glial cells are binucleate. In addition, confocal time-lapse imaging of mitoses at the VZ surface shows that citron kinase is also necessary for phases of the cell cycle just prior to cytokinesis. Deficits in mitosis seen in mutants indicate aberrant mitotic spindle function, and like deficits in cytokinesis, occur in some but not all cells at the VZ surface. Citron kinase is therefore an essential multifunctional regulator of cell divisions in the VZ, and may serve to coordinate chromosome segregation with cytokinesis in neuronal precursors.
与所有正在分裂的细胞一样,新皮质脑室区(VZ)的神经祖细胞成功进行细胞分裂,关键取决于在有丝分裂过程中协调染色体分离与胞质分裂。这种协调进一步表明,常见的分子调节因子可能将有丝分裂事件与胞质分裂事件联系起来。最近的遗传学证据表明,中枢神经系统神经元祖细胞的胞质分裂需要柠檬激酶的功能,但身体的大多数其他细胞类型则不需要。在新皮质中,柠檬激酶对神经源性胞质分裂最为关键。在柠檬激酶基因敲除突变体中,新皮质内很大一部分神经元细胞是双核的;然而,很少有胶质细胞是双核的。此外,对VZ表面有丝分裂的共聚焦延时成像显示,柠檬激酶对于胞质分裂之前的细胞周期阶段也是必需的。突变体中观察到的有丝分裂缺陷表明有丝分裂纺锤体功能异常,并且与胞质分裂缺陷一样,发生在VZ表面的一些但不是所有细胞中。因此,柠檬激酶是VZ中细胞分裂必不可少的多功能调节因子,可能有助于协调神经元前体细胞中染色体分离与胞质分裂。