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

J Cell Biol. 2017 Dec 4;216(12):4313-4330. doi: 10.1083/jcb.201704157. Epub 2017 Oct 31.

Abstract

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.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Animals, Newborn
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement
  • Embryo, Mammalian
  • GTPase-Activating Proteins
  • Gene Expression Regulation, Developmental
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Myosin-Light-Chain Phosphatase / genetics*
  • Myosin-Light-Chain Phosphatase / metabolism
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Primary Cell Culture
  • Prosencephalon / cytology
  • Prosencephalon / growth & development
  • Prosencephalon / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • rho GTP-Binding Proteins / genetics*
  • rho GTP-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein

Substances

  • Actins
  • Dock7 protein, mouse
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Proto-Oncogene Proteins c-akt
  • Myosin-Light-Chain Phosphatase
  • RhoA protein, mouse
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein