Heterogeneous nuclear ribonucleoprotein A3a controls mitotic progression of neural progenitors via interaction with cohesin

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.