Open AccessHeterogeneous nuclear ribonucleoprotein A3a controls mitotic progression of neural progenitors via interaction with cohesin
Author(s) -
Min-Yi Ou,
Xiang-Chun Ju,
Yijun Cai,
Xin-Yao Sun,
Junfeng Wang,
Xiu-Qing Fu,
Qiang Sun,
Zhen-Ge Luo
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.185132
Subject(s) - biology , neurogenesis , mitosis , microbiology and biotechnology , neural stem cell , ribonucleoprotein , cohesin , downregulation and upregulation , heterogeneous nuclear ribonucleoprotein , progenitor cell , cell division , genetics , stem cell , chromosome , cell , gene , rna
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 of 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 highly expressed in NPs of mouse and human cortex at early stages with a unique peri-chromosome pattern. Intriguingly, down-regulation 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, down-regulation of HNRNPA3 in cultured human cerebral organoids led to marked reduction in NPs and deep-layer neurons. Thus, this study has identified a critical role of HNRNPA3 in NP division and highlighted the relationship between mitosis progression and early neurogenesis.