title: A radial glia-specific role of RhoA in double cortex formation.
abstract: The positioning of neurons in the cerebral cortex is of crucial importance for its function as highlighted by the severe consequences of migrational disorders in patients. Here we show that genetic deletion of the small GTPase RhoA in the developing cerebral cortex results in two migrational disorders: subcortical band heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when transplanted into wild-type cerebral cortex, whereas the converse was not the case. Alterations in the radial glia scaffold are demonstrated to cause these migrational defects through destabilization of both the actin and the microtubules cytoskeleton. These data not only demonstrate that RhoA is largely dispensable for migration in neurons but also showed that defects in radial glial cells, rather than neurons, can be sufficient to produce SBH.
authors.affiliation: Helmholtz Center Munich, German Research Center for Environmental Health, Institute for Stem Cell Research, 85764 Neuherberg, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cappello
authors.forename: Christian R J
authors.initials: CR
authors.lastname: Böhringer
authors.forename: Matteo
authors.initials: M
authors.lastname: Bergami
authors.forename: Karl-Klaus
authors.initials: KK
authors.lastname: Conzelmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Ghanem
authors.forename: Giulio Srubek
authors.initials: GS
authors.lastname: Tomassy
authors.forename: Paola
authors.initials: P
authors.lastname: Arlotta
authors.forename: Marco
authors.initials: M
authors.lastname: Mainardi
authors.forename: Manuela
authors.initials: M
authors.lastname: Allegra
authors.forename: Matteo
authors.initials: M
authors.lastname: Caleo
authors.forename: Jolanda
authors.initials: J
authors.lastname: van Hengel
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000502:physiology* / Q000637:transplantation; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018274:Electroporation; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology / Q000637:transplantation; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D011247:Pregnancy; D016622:Silver Staining; D020742:rhoA GTP-Binding Protein / Q000172:deficiency* / Q000235:genetics
chemical_list: D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D020742:rhoA GTP-Binding Protein; D001973:Bromodeoxyuridine