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KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development

ABSTRACT: Balanced symmetric and asymmetric divisions of neural progenitor cells (NPCs) are crucial for orderly progression of brain development, but the underlying mechanisms are not fully understood. Here, we report that mitotic kinesin KIF20A/MKLP2 interacts with RGS3 and plays a crucial role in controlling the division modes of NPCs during the mouse cortical neurogenesis. KIF20A is selectively expressed by daughter progenitors in NPC divisions. Knockdown of KIF20A causes dislocation of RGS3 from the intercellular bridge (ICB) of dividing NPCs, impairs the function of EphrinB-RGS cell fate signaling complex, and leads to a transition in NPCs from proliferative to differentiative divisions. Germ-line and inducible knockout of KIF20A causes a loss of progenitor cells and neurons and results in thinner cortex and ventriculomegaly. Interestingly, loss-of-function of KIF20A induces early cell cycle exit and precocious neuronal differentiation without causing substantial multinucleation or apoptosis in mutant NPCs. Our results thus uncover a novel RGS-KIF20A axis in regulation of cell division mode and suggest a potential link of cytokinesis control within the ICB to regulation of cell fate determination.

ORGANISM(S): Mus musculus

PROVIDER: GSE108624 | GEO | 2018/05/14

REPOSITORIES: GEO

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KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development

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