Rnd3 coordinates early steps of cortical neurogenesis through actin-dependent and -independent mechanisms.
Nat Commun. 2013-03-27; 4(1):
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1. Nat Commun. 2013;4:1635. doi: 10.1038/ncomms2614.
Rnd3 coordinates early steps of cortical neurogenesis through actin-dependent and
Pacary E(1), Azzarelli R, Guillemot F.
(1)Division of Molecular Neurobiology, MRC National Institute for Medical
Research, London, UK.
The generation of neurons by neural stem cells is a highly choreographed process
that requires extensive and dynamic remodelling of the cytoskeleton at each step
of the process. The atypical RhoGTPase Rnd3 is expressed by progenitors in the
embryonic brain but its role in early steps of neurogenesis has not been
addressed. Here we show that silencing Rnd3 in the embryonic cerebral cortex
interferes with the interkinetic nuclear migration of radial glial stem cells,
disrupts their apical attachment and modifies the orientation of their cleavage
plane. These defects are rescued by co-expression of a constitutively active form
of cofilin, demonstrating that Rnd3-mediated disassembly of actin filaments
coordinates the cellular behaviour of radial glial. Rnd3 also limits the
divisions of basal progenitors via a distinct mechanism involving the suppression
of cyclin D1 translation. Interestingly, although Rnd3 expression is controlled
transcriptionally by Ascl1, this proneural factor is itself required in radial
glial progenitors only for proper orientation of cell divisions.
PMID: 23535656 [Indexed for MEDLINE]