SEPT7 Interacts with KIF20A and Regulates the Proliferative State of Neural Progenitor Cells During Cortical Development

被引:18
|
作者
Qiu, Runxiang [1 ]
Geng, Anqi [1 ,2 ]
Liu, Jiancheng [1 ]
Xu, C. Wilson [3 ]
Menon, Manoj B. [4 ,5 ]
Gaestel, Matthias [4 ]
Lu, Qiang [1 ]
机构
[1] City Hope Natl Med Ctr, Beckman Res Inst, Dept Dev & Stem Cell Biol, Duarte, CA 91010 USA
[2] Northwestern Polytech Univ, Inst Med Res, Xian, Shaanxi, Peoples R China
[3] Balto Pharmaceut Inc, South Pasadena, CA 91030 USA
[4] Hannover Med Sch, Inst Cell Biochem, D-30625 Hannover, Germany
[5] Indian Inst Technol Delhi, Kusuma Sch Biol Sci, New Delhi 110016, India
基金
美国国家卫生研究院;
关键词
cerebral cortical development; KIF20A; neural progenitor cells; proliferation versus differentiation; SEPT7; CEREBRAL-CORTEX; EVOLUTION; NEURONS; PROTEIN; MORPHOGENESIS; LOCALIZATION; ASYMMETRY; COMPONENT; BIOLOGY; GTPASES;
D O I
10.1093/cercor/bhz292
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Balanced proliferation and differentiation of neural progenitor cells (NPCs) are critical for brain development, but how the process is regulated and what components of the cell division machinery is involved are not well understood. Here we report that SEPT7, a cell division regulator originally identified in Saccharomyces cerevisiae, interacts with KIF20A in the intercellular bridge of dividing NPCs and plays an essential role in maintaining the proliferative state of NPCs during cortical development. Knockdown of SEPT7 in NPCs results in displacement of KIF20A from the midbody and early neuronal differentiation. NPC-specific inducible knockout of Sept7 causes early cell cycle exit, precocious neuronal differentiation, and ventriculomegaly in the cortex, but surprisingly does not lead to noticeable cytokinesis defect. Our data uncover an interaction of SEPT7 and KIF20A during NPC divisions and demonstrate a crucial role of SEPT7 in cell fate determination. In addition, this study presents a functional approach for identifying additional cell fate regulators of the mammalian brain.
引用
收藏
页码:3030 / 3043
页数:14
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