Citron kinase is a regulator of mitosis and neurogenic cytokinesis in the neocortical ventricular zone

Citron kinase is a regulator of mitosis and neurogenic cytokinesis in the neocortical ventricular zone
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DOI:
10.1093/cercor/13.6.588
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发表时间:
2003-06-01
期刊:
影响因子:
3.7
通讯作者:
Bai, JL
Bai, JL
中科院分区:
医学2区
文献类型:
--
作者:
LoTurco, JJ;Sarkisian, MR;Bai, JL

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新皮质脑室区神经前体细胞的成功分裂,就像所有分裂细胞一样,关键取决于有丝分裂过程中染色体分离与胞质分裂的协调。这种协调进一步表明,共同的分子调节因子可能将有丝分裂中的事件与细胞质分裂中的事件联系起来。最近的遗传学证据表明,在中枢神经系统神经前体细胞的胞质分裂,而不是在身体的大多数其他类型的细胞中,需要柠檬酸激酶的功能。在新皮质中,柠檬酸激酶对神经源性胞质分裂最为关键。在柠檬酸激酶缺失突变体中,新皮质内很大比例的神经细胞是双核的;然而,很少有胶质细胞是双核的。此外,VZ表面有丝分裂的共聚焦时间推移成像显示,在细胞质分裂之前的细胞周期的各个阶段,柠檬酸激酶也是必需的。突变体中发现的有丝分裂缺陷表明有丝分裂纺锤体功能异常,类似于胞质分裂缺陷,出现在VZ表面的一些但不是所有细胞中。因此,Citron Kinase是VZ细胞分裂的重要多功能调节器,并可能用于协调神经元前体中的染色体分离和胞质分裂。
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.