title: Control of outer radial glial stem cell mitosis in the human brain.
abstract: Evolutionary expansion of the human neocortex is partially attributed to a relative abundance of neural stem cells in the fetal brain called outer radial glia (oRG). oRG cells display a characteristic division mode, mitotic somal translocation (MST), in which the soma rapidly translocates toward the cortical plate immediately prior to cytokinesis. MST may be essential for progenitor zone expansion, but the mechanism of MST is unknown, hindering exploration of its function in development and disease. Here, we show that MST requires activation of the Rho effector ROCK and nonmuscle myosin II, but not intact microtubules, centrosomal translocation into the leading process, or calcium influx. MST is independent of mitosis and distinct from interkinetic nuclear migration and saltatory migration. Our findings suggest that disrupted MST may underlie neurodevelopmental diseases affecting the Rho-ROCK-myosin pathway and provide a foundation for future exploration of the role of MST in neocortical development, evolution, and disease.
authors.affiliation: Department of Neurology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California, San Francisco, 1550 4th Street, San Francisco, CA 94158, USA.
authors.forename: Bridget E L
authors.initials: BE
authors.lastname: Ostrem
authors.affiliation: Department of Neurology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Lui
authors.affiliation: Department of Neurology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California, San Francisco, 1550 4th Street, San Francisco, CA 94158, USA.
authors.forename: Caitlyn C
authors.initials: CC
authors.lastname: Gertz
authors.affiliation: Department of Neurology, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA. Electronic address: kriegsteina@stemcell.ucsf.edu.
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Kriegstein
mesh_terms: D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D005333:Fetus; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D024462:Myosin Type II / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D054460:rho-Associated Kinases; D024462:Myosin Type II; D002118:Calcium
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