TY - JOUR
T1 - Coupling of cell migration with neurogenesis by proneural bHLH factors
AU - Ge, Weihong
AU - He, Fei
AU - Kim, Kevin J
AU - Blanchi, Bruno
AU - Coskun, Volkan
AU - Nguyen, Laurent
AU - Wu, Xiangbing
AU - Zhao, Jing
AU - Heng, Julian Ik-Tsen
AU - Martinowich, Keri
AU - Tao, Jifang
AU - Wu, Hao
AU - Castro, Diogo
AU - Sobeih, Magdi M
AU - Corfas, Gabriel
AU - Gleeson, Joseph G
AU - Greenberg, Michael E
AU - Guillemot, Francois
AU - Sun, Yi E
PY - 2006/1/31
Y1 - 2006/1/31
N2 - 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.
AB - 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.
KW - Actins/chemistry
KW - Animals
KW - Basic Helix-Loop-Helix Transcription Factors/metabolism
KW - Blotting, Western
KW - Cell Differentiation
KW - Cell Movement
KW - Cerebral Cortex/pathology
KW - Chromatin Immunoprecipitation
KW - Cytoskeleton/metabolism
KW - DNA/chemistry
KW - DNA-Binding Proteins/chemistry
KW - Doublecortin Domain Proteins
KW - Down-Regulation
KW - Electroporation
KW - GTP Phosphohydrolases/metabolism
KW - Gene Expression Regulation
KW - Mice
KW - Mice, Transgenic
KW - Microscopy, Fluorescence
KW - Microtubule-Associated Proteins/biosynthesis
KW - Microtubules/metabolism
KW - Mutation
KW - Nerve Tissue Proteins/biosynthesis
KW - Neurons/metabolism
KW - Neuropeptides/biosynthesis
KW - Protein Binding
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Transcription Factors/chemistry
KW - Transfection
KW - Up-Regulation
KW - rhoA GTP-Binding Protein/metabolism
U2 - 10.1073/pnas.0510419103
DO - 10.1073/pnas.0510419103
M3 - Article
C2 - 16432194
SN - 0027-8424
VL - 103
SP - 1319
EP - 1324
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -