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Nat Neurosci. 2012 Sep;15(9):1201-10. doi: 10.1038/nn.3171. Epub 2012 Jul 29.

DOCK7 interacts with TACC3 to regulate interkinetic nuclear migration and cortical neurogenesis.

Author information

1
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.

Abstract

Neurogenesis in the developing neocortex relies on the ability of radial glial progenitor cells (RGCs) to switch from proliferative to differentiative neuron-generating divisions, but the molecular mechanisms that control this switch in a correct temporal manner are not well understood. Here, we show that DOCK7, a member of the DOCK180 family of proteins, regulates RGC proliferation versus differentiation. Silencing of DOCK7 in RGCs of developing mouse embryos impedes neuronal differentiation and maintains cells as cycling progenitors. In contrast, DOCK7 overexpression promotes RGC differentiation to basal progenitors and neurons. We further present evidence that DOCK7 influences neurogenesis by controlling apically directed interkinetic nuclear migration of RGCs. DOCK7 exerts its effects by antagonizing the microtubule growth-promoting function of the centrosome-associated protein TACC3. Thus, DOCK7 interaction with TACC3 controls interkinetic nuclear migration and the genesis of neurons from RGCs during cortical development.

PMID:
22842144
PMCID:
PMC3431462
DOI:
10.1038/nn.3171
[Indexed for MEDLINE]
Free PMC Article

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