Abstract

Balanced symmetric and asymmetric divisions of neural progenitor cells (NPCs) are crucial for brain development, but the underlying mechanisms are not fully understood. Here we report that mitotic kinesin KIF20A/MKLP2 interacts with RGS3 and plays a crucial role in controlling the division modes of NPCs during cortical neurogenesis. Knockdown of KIF20A in NPCs causes dislocation of RGS3 from the intercellular bridge (ICB), impairs the function of Ephrin-B–RGS cell fate signaling complex, and leads to a transition from proliferative to differentiative divisions. Germline and inducible knockout of KIF20A causes a loss of progenitor cells and neurons and results in thinner cortex and ventriculomegaly. Interestingly, loss of function of KIF20A induces early cell cycle exit and precocious neuronal differentiation without causing substantial cytokinesis defect or apoptosis. Our results identify a RGS–KIF20A axis in the regulation of cell division and suggest a potential link of the ICB to regulation of cell fate determination.

Details

Title
KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development
Author
Geng, Anqi 1 ; Qiu, Runxiang 1 ; Murai, Kiyohito 2 ; Liu, Jiancheng 1 ; Wu, Xiwei 3 ; Zhang, Heying 1 ; Farhoodi, Henry 1 ; Duong, Nam 1 ; Jiang, Meisheng 4 ; Yee, Jiing-kuan 5 ; Tsark, Walter 6 ; Lu, Qiang 1   VIAFID ORCID Logo 

1  Department of Developmental and Stem Cell Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA 
2  Department of Developmental and Stem Cell Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA; Department of Anatomy and Neurobiology, Nagasaki University School of Medicine, Nagasaki, Japan 
3  Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA 
4  Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA 
5  Department of Virology, Beckman Research Institute of the City of Hope, Duarte, CA, USA 
6  Transgenic/Knockout Mice Facility, Beckman Research Institute of the City of Hope, Duarte, CA, USA 
Pages
1-16
Publication year
2018
Publication date
Jul 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-05152-1
ProQuest document ID
2069382406
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.