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.
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| http://dx.doi.org/10.1038/nn.3171 | DOI Listing |
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Article Synopsis
- At the end of cell division, the nuclear envelope reforms around chromosomes, and female meiosis involves two cell divisions (meiosis I and II) separated by a phase called interkinesis.
- Previous assumptions held that the nuclear envelope doesn't reassemble during interkinesis due to the lack of chromosome decondensation and genome replication.
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