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Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

The Journal of cell biology | 2017

Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS.

Pubmed ID: 29089377 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA045508
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH082808
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS082266
  • Agency: NCI NIH HHS, United States
    Id: T32 CA148056

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