title: Coupling of cell migration with neurogenesis by proneural bHLH factors.
abstract: After cell birth, almost all neurons in the mammalian central nervous system migrate. It is unclear whether and how cell migration is coupled with neurogenesis. Here we report that proneural basic helix-loop-helix (bHLH) transcription factors not only initiate neuronal differentiation but also potentiate cell migration. Mechanistically, proneural bHLH factors regulate the expression of genes critically involved in migration, including down-regulation of RhoA small GTPase and up-regulation of doublecortin and p35, which, in turn, modulate the actin and microtubule cytoskeleton assembly and enable newly generated neurons to migrate. In addition, we report that several DNA-binding-deficient proneural genes that fail to initiate neuronal differentiation still activate migration, whereas a different mutation of a proneural gene that causes a failure in initiating cell migration still leads to robust neuronal differentiation. Collectively, these data suggest that transcription programs for neurogenesis and migration are regulated by bHLH factors through partially distinct mechanisms.
authors.affiliation: Mental Retardation Research Center, Dept. of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, David Geffen School of Medicine, University of California-Los Angeles, 635 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
authors.forename: Weihong
authors.initials: W
authors.lastname: Ge
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kim
authors.forename: Bruno
authors.initials: B
authors.lastname: Blanchi
authors.forename: Volkan
authors.initials: V
authors.lastname: Coskun
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
authors.forename: Xiangbing
authors.initials: X
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Julian Ik-Tsen
authors.initials: JI
authors.lastname: Heng
authors.forename: Keri
authors.initials: K
authors.lastname: Martinowich
authors.forename: Jifang
authors.initials: J
authors.lastname: Tao
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Diogo
authors.initials: D
authors.lastname: Castro
authors.forename: Magdi M
authors.initials: MM
authors.lastname: Sobeih
authors.forename: Gabriel
authors.initials: G
authors.lastname: Corfas
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Gleeson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Greenberg
authors.forename: Francois
authors.initials: F
authors.lastname: Guillemot
authors.forename: Yi E
authors.initials: YE
authors.lastname: Sun
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement; D002540:Cerebral Cortex / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D000089622:Doublecortin Domain Proteins; D015536:Down-Regulation; D018274:Electroporation; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D000089622:Doublecortin Domain Proteins; D020558:GTP Phosphohydrolases; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D014157:Transcription Factors; D020742:rhoA GTP-Binding Protein; C089495:neuronal Cdk5 activator (p25-p35); C093564:Neurogenic differentiation factor 1