Cytoskeletal Associated Filamin A and RhoA Affect Neural Progenitor Specification During Mitosis.

Neural progenitor proliferation and cell fate decision from self-renewal to differentiation are crucial factors in determining brain size and morphology. The cytoskeletal dependent regulation of these processes is not entirely known. The actin-binding filamin A (FlnA) was shown to regulate proliferation of progenitors by directing changes in cell cycles proteins such as Cdk1 during G2/M phase. Here we report that functional loss of FlnA not only affects the rate of proliferation by altering cell cycle length but also causes a defect in early differentiation through changes in cell fate specification. FlnA interacts with Rho GTPase RhoA, and FlnA loss impairs RhoA activation. Disruption of either of these cytoskeletal associated proteins delays neurogenesis and promotes neural progenitors to remain in proliferative states. Aurora kinase B (Aurkb) has been implicated in cytokinesis, and peaks in expression during the G2/M phase. Inhibition of FlnA or RhoA impairs Aurkb degradation and alters its localization during mitosis. Overexpression of Aurkb replicates the same delay in neurogenesis seen with loss of FlnA or RhoA. Our findings suggest that shared cytoskeletal processes can direct neural progenitor proliferation by regulating the expression and localization of proteins that are implicated in the cell cycle progression and cell fate specification.

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