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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antimetabolites
-
Bromodeoxyuridine
-
Carrier Proteins / genetics
-
Carrier Proteins / physiology*
-
Cell Line
-
Cell Movement / physiology*
-
Cell Nucleus / physiology
-
Cell Proliferation
-
Centrosome / physiology
-
Cerebral Cortex / growth & development*
-
DNA / genetics
-
Electroporation
-
Female
-
Fetal Proteins / genetics
-
Fetal Proteins / physiology*
-
GTPase-Activating Proteins
-
Guanine Nucleotide Exchange Factors / genetics
-
Guanine Nucleotide Exchange Factors / physiology*
-
Immunohistochemistry
-
Mice
-
Microtubule-Associated Proteins
-
Microtubules / physiology
-
Neocortex / growth & development
-
Neocortex / physiology
-
Neural Stem Cells
-
Neurogenesis / genetics
-
Neurogenesis / physiology*
-
Neuroglia / physiology
-
Pregnancy
-
Transfection
Substances
-
Antimetabolites
-
Carrier Proteins
-
Dock7 protein, mouse
-
Fetal Proteins
-
GTPase-Activating Proteins
-
Guanine Nucleotide Exchange Factors
-
Microtubule-Associated Proteins
-
TACC3 protein, mouse
-
DNA
-
Bromodeoxyuridine