title: Crucial roles of the Arp2/3 complex during mammalian corticogenesis.
abstract: The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex - the unique actin nucleator that produces branched actin networks - plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in murine RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with an abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly might be particularly important for neuronal cell motility in a soft or poorly adhesive matrix environment.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Wang
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Chou
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Sreekumar
authors.initials: S
authors.lastname: Ramachandran
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xia
authors.affiliation: Lieber Institute for Brain Development, 855 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Huei-Ying
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Fengli
authors.initials: F
authors.lastname: Guo
authors.affiliation: Division of Hematology/Oncology, Robert Lurie Comprehensive Cancer Center, Department of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Praveen
authors.initials: P
authors.lastname: Suraneni
authors.affiliation: Lieber Institute for Brain Development, 855 North Wolfe Street, Baltimore, MD 21205, USA Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, 4940 Eastern Ave., Baltimore, MD 21224, USA Department of Neuroscience, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Brady J
authors.initials: BJ
authors.lastname: Maher
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA Department of Cell Biology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles St., Baltimore, MD 21218, USA rong@jhu.edu.
authors.forename: Rong
authors.identifier: 0000-0001-9835-6563
authors.initials: R
authors.lastname: Li
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D063928:Ependymoglial Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex
keywords: Actin; Arp2/3 complex; Cortical development; Mouse; Neurogenesis; Neuronal migration; Radial glia