Heterogeneous nuclear ribonucleoprotein A3 controls mitotic progression of neural progenitors via interaction with cohesin.

Autor:	Ou MY; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Ju XC; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China., Cai YJ; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China., Sun XY; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Wang JF; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Fu XQ; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Sun Q; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China., Luo ZG; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China luozhg@shanghaitech.edu.cn.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2020 May 15; Vol. 147 (10). Date of Electronic Publication: 2020 May 15.
DOI:	10.1242/dev.185132
Abstrakt:	Cortex development is controlled by temporal patterning of neural progenitor (NP) competence with sequential generation of deep and superficial layer neurons, but underlying mechanisms remain elusive. Here, we report a role for heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in regulating the division of early cortical NPs that mainly give rise to deep-layer neurons via direct neurogenesis. HNRNPA3 is expressed at high levels in NPs of mouse and human cortex at early stages, with a unique peri-chromosome pattern. Intriguingly, downregulation of HNRNPA3 caused chromosome disarrangement, which hindered normal separation of chromosomes during NP division, leading to mitotic delay. Furthermore, HNRNPA3 is associated with the cohesin-core subunit SMC1A and controls its association with chromosomes, implicating a mechanism for the role of HNRNPA3 in regulating chromosome segregation in dividing NPs. Hnrnpa3 -deficient mice exhibited reduced cortical thickness, especially of deep layers. Moreover, downregulation of HNRNPA3 in cultured human cerebral organoids led to marked reduction in NPs and deep-layer neurons. Thus, this study has identified a crucial role for HNRNPA3 in NP division and highlighted the relationship between mitosis progression and early neurogenesis. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu