The heterogeneous nuclear ribonucleoprotein K is responsible for regulating the fate decisions of neural precursor cells of the developing cerebral cortex

Neurogenesis within the developing cortex occurs as a result of the controlled differentiation of neural precursor cells (NPCs), achieved by tightly regulated gene expression. Many RNA-binding proteins have been implicated in regulating gene expression throughout development, including the heterogeneous nuclear ribonucleoproteins (hnRNPs). Specifically, mutation of hnRNP-K has been identified in Kabuki-like syndrome, a neurodevelopmental disorder presenting with cortical atrophy, ventriculomegaly, and periventricular nodular heterotopia. This research validates hnRNP-K expression throughout the neurogenic period of cortical development and demonstrates a critical role for hnRNP-K in the cell fate decisions of NPCs. Knockdown of hnRNP-K in vitro resulted in a significant increase in the proportion of β3T+ neurons and a significant decrease in the proportion of Nestin+ NPCs. Immunoprecipitation revealed hnRNP-K maintains RNA-based interactions with proteins known to regulate gene expression, proliferation and differentiation. Collectively, these findings demonstrate a significant role for hnRNP-K in maintenance of NPC phenotype during murine cortical development.