1. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain
- Author
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Yilin Tai, Nicholas B. Gallo, Jia Ray Yu, Shinichi Nakamuta, Yu-Ting Yang, Chia-Lin Wang, and Linda Van Aelst
- Subjects
rho GTP-Binding Proteins ,0301 basic medicine ,Rostral migratory stream ,Cellular differentiation ,Primary Cell Culture ,Biology ,Microtubules ,Article ,Mice ,Myosin-Light-Chain Phosphatase ,03 medical and health sciences ,Prosencephalon ,Neuroblast ,Cell Movement ,Cell Line, Tumor ,Neuroblast migration ,Somal translocation ,Animals ,Guanine Nucleotide Exchange Factors ,Humans ,reproductive and urinary physiology ,Research Articles ,Neurons ,GTPase-Activating Proteins ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,Anatomy ,Embryo, Mammalian ,Actins ,Olfactory bulb ,Cell biology ,HEK293 Cells ,030104 developmental biology ,Animals, Newborn ,nervous system ,embryonic structures ,Forebrain ,rhoA GTP-Binding Protein ,Proto-Oncogene Proteins c-akt ,Ganglion mother cell ,HeLa Cells ,Signal Transduction - Abstract
Neuroblasts born postnatally in the ventricular–subventricular zone migrate long distances via the rostral migratory stream (RMS) to the olfactory bulb. Nakamuta et al. show that DOCK7 drives tangential migration of neuroblasts in the RMS by controlling both leading process extension and somal translocation through Rac-dependent and myosin phosphatase–RhoA–interacting protein-dependent pathways, respectively., 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.
- Published
- 2017
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