Maintaining neural stem and progenitor cell pools in the developing cortex
The kinesin-like motor protein KIF23 is a critical component of the mitotic central spindle. This study uncovers a role of KIF23 in maintaining neural stem and progenitor cells (NSPCs) during cortical development, offering insights into the mechanisms of microcephaly pathogenesis.
Generation of progenitors and mature neurons involve accurate mitotic division of neural stem and progenitor cells (NSPCs). Although microcephaly in humans have been linked to mutations in the kinesin-like motor protein KIF23 gene, the mechanisms remain not well understood.
The authors show that Kif23/KIF23 is expressed in NSPCs in the embryonic cortex of mice, ferrets, and humans.
knockdown of Kif23 results in precocious neurogenesis, neuronal apoptosis, and activation of the γ-H2AX-p53 signaling pathway. It also disrupts mitotic spindle orientation, cytokinesis, and the integrity of the apical structure in NSPCs.
The authors found that microcephaly-associated mutant KIF23 fails to rescue the phenotypes induced by Kif23 knockdown in mice.
https://www.embopress.org/doi/full/10.1038/s44318-024-00327-7
