A Radial Glia-Specific Role of RhoA in Double Cortex Formation
Copyright policy )A Radial Glia-Specific Role of RhoA in Double Cortex Formation
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.
- University of Copenhagen Denmark
- National Research Council Italy
- University of Copenhagen Denmark
- University of Padua Italy
- University of Copenhagen
Silver Staining, glia, Neuroscience(all), Age Factors; Animals; Animals, Newborn; Bromodeoxyuridine; Cell Movement; Cell Proliferation; Cerebral Cortex; Classical Lissencephalies and Subcortical Band Heterotopias; Disease Models, Animal; Electroporation; Embryo, Mammalian; Embryonic Stem Cells; Female; GAP-43 Protein; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; In Vitro Techniques; Mice; Mice, Transgenic; Nerve Tissue Proteins; Neuroglia; Neurons; Pregnancy; Silver Staining; rhoA GTP-Binding Protein, Green Fluorescent Proteins, Age Factors; Animals; Animals; Newborn; Bromodeoxyuridine; Cell Movement; Cell Proliferation; Cerebral Cortex; Classical Lissencephalies and Subcortical Band Heterotopias; Disease Models; Animal; Electroporation; Embryo; Mammalian; Embryonic Stem Cells; Female; GAP-43 Protein; Gene Expression Regulation; Developmental; Green Fluorescent Proteins; In Vitro Techniques; Mice; Mice; Transgenic; Nerve Tissue Proteins; Neuroglia; Neurons; Pregnancy; Silver Staining; rhoA GTP-Binding Protein, brain development, Mice, Transgenic, Nerve Tissue Proteins, Classical Lissencephalies and Subcortical Band Heterotopias, In Vitro Techniques, Transgenic, Mice, GAP-43 Protein, Pregnancy, Cell Movement, Animals, Developmental, Embryonic Stem Cells, Cell Proliferation, Neurons, Cerebral Cortex, Animal, Mammalian, Bnormal neuronal migration; Outer subventricular zone; Serum response factor; Cerebral-cortex; Cell-migration; Visual-cortex; Pyramidal neurons; Progenitor cells; CRE recombinase; in-vivo, Age Factors, Gene Expression Regulation, Developmental, RhoA, Newborn, Embryo, Mammalian, Disease Models, Animal, Electroporation, Gene Expression Regulation, Animals, Newborn, Bromodeoxyuridine, Embryo, Disease Models, Female, rhoA GTP-Binding Protein, Neuroglia
Silver Staining, glia, Neuroscience(all), Age Factors; Animals; Animals, Newborn; Bromodeoxyuridine; Cell Movement; Cell Proliferation; Cerebral Cortex; Classical Lissencephalies and Subcortical Band Heterotopias; Disease Models, Animal; Electroporation; Embryo, Mammalian; Embryonic Stem Cells; Female; GAP-43 Protein; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; In Vitro Techniques; Mice; Mice, Transgenic; Nerve Tissue Proteins; Neuroglia; Neurons; Pregnancy; Silver Staining; rhoA GTP-Binding Protein, Green Fluorescent Proteins, Age Factors; Animals; Animals; Newborn; Bromodeoxyuridine; Cell Movement; Cell Proliferation; Cerebral Cortex; Classical Lissencephalies and Subcortical Band Heterotopias; Disease Models; Animal; Electroporation; Embryo; Mammalian; Embryonic Stem Cells; Female; GAP-43 Protein; Gene Expression Regulation; Developmental; Green Fluorescent Proteins; In Vitro Techniques; Mice; Mice; Transgenic; Nerve Tissue Proteins; Neuroglia; Neurons; Pregnancy; Silver Staining; rhoA GTP-Binding Protein, brain development, Mice, Transgenic, Nerve Tissue Proteins, Classical Lissencephalies and Subcortical Band Heterotopias, In Vitro Techniques, Transgenic, Mice, GAP-43 Protein, Pregnancy, Cell Movement, Animals, Developmental, Embryonic Stem Cells, Cell Proliferation, Neurons, Cerebral Cortex, Animal, Mammalian, Bnormal neuronal migration; Outer subventricular zone; Serum response factor; Cerebral-cortex; Cell-migration; Visual-cortex; Pyramidal neurons; Progenitor cells; CRE recombinase; in-vivo, Age Factors, Gene Expression Regulation, Developmental, RhoA, Newborn, Embryo, Mammalian, Disease Models, Animal, Electroporation, Gene Expression Regulation, Animals, Newborn, Bromodeoxyuridine, Embryo, Disease Models, Female, rhoA GTP-Binding Protein, Neuroglia
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