title: Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex.
abstract: The molecular mechanisms specifying the dendritic morphology of different neuronal subtypes are poorly understood. Here we demonstrate that the bHLH transcription factor Neurogenin2 (Ngn2) is both necessary and sufficient for specifying the dendritic morphology of pyramidal neurons in vivo by specifying the polarity of its leading process during the initiation of radial migration. The ability of Ngn2 to promote a polarized leading process outgrowth requires the phosphorylation of a single tyrosine residue at position 241, an event that is neither involved in Ngn2 direct transactivation properties nor its proneural function. Interestingly, the migration defect observed in the Ngn2 knockout mouse and in progenitors expressing the Ngn2(Y241F) mutation can be rescued by inhibiting the activity of the small-GTPase RhoA in cortical progenitors. Our results demonstrate that Ngn2 coordinates the acquisition of the radial migration properties and the unipolar dendritic morphology characterizing pyramidal neurons through molecular mechanisms distinct from those mediating its proneural activity.
authors.affiliation: Department of Phamacology, Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Randal
authors.initials: R
authors.lastname: Hand
authors.forename: Dante
authors.initials: D
authors.lastname: Bortone
authors.forename: Pierre
authors.initials: P
authors.lastname: Mattar
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
authors.forename: Julian Ik-Tsen
authors.initials: JI
authors.lastname: Heng
authors.forename: Sabrice
authors.initials: S
authors.lastname: Guerrier
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Boutt
authors.forename: Eldon
authors.initials: E
authors.lastname: Peters
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Barnes
authors.forename: Carlos
authors.initials: C
authors.lastname: Parras
authors.forename: Carol
authors.initials: C
authors.lastname: Schuurmans
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
authors.forename: Franck
authors.initials: F
authors.lastname: Polleux
mesh_terms: D000367:Age Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002645:Chickens; D003001:Cloning, Molecular / Q000379:methods; D003712:Dendrites / Q000502:physiology*; D016521:Electrophoresis, Gel, Pulsed-Field / Q000379:methods; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D019579:Neocortex / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D017966:Pyramidal Cells / Q000166:cytology* / Q000502:physiology*; D016415:Sequence Alignment; D013234:Stem Cells / Q000502:physiology; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D014404:Tubulin; D014443:Tyrosine; D020742:rhoA GTP-Binding Protein; C079240:Mtap2 protein, mouse; C102938:Neurog2 protein, mouse; C462941:beta3 tubulin, mouse