Coupling of cell migration with neurogenesis by proneural bHLH factors.
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.
Ge
Weihong
W
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.
He
Fei
F
Kim
Kevin J
KJ
Blanchi
Bruno
B
Coskun
Volkan
V
Nguyen
Laurent
L
Wu
Xiangbing
X
Zhao
Jing
J
Heng
Julian Ik-Tsen
JI
Martinowich
Keri
K
Tao
Jifang
J
Wu
Hao
H
Castro
Diogo
D
Sobeih
Magdi M
MM
Corfas
Gabriel
G
Gleeson
Joseph G
JG
Greenberg
Michael E
ME
Guillemot
Francois
F
Sun
Yi E
YE
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
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