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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / chemistry
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Blotting, Western
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Cell Differentiation
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Cell Movement
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Cerebral Cortex / pathology
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Chromatin Immunoprecipitation
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Cytoskeleton / metabolism
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DNA / chemistry
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / physiology*
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Doublecortin Domain Proteins
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Down-Regulation
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Electroporation
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GTP Phosphohydrolases / metabolism
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Gene Expression Regulation*
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Mice
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Mice, Transgenic
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Microscopy, Fluorescence
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Microtubule-Associated Proteins / biosynthesis
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Microtubules / metabolism
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Mutation
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / metabolism
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Neurons / metabolism*
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Neuropeptides / biosynthesis
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Protein Binding
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / chemistry*
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Transcription Factors / physiology*
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Transfection
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Up-Regulation
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rhoA GTP-Binding Protein / metabolism
Substances
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Actins
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Doublecortin Domain Proteins
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Neuropeptides
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Transcription Factors
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neuronal Cdk5 activator (p25-p35)
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Neurogenic differentiation factor 1
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DNA
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GTP Phosphohydrolases
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rhoA GTP-Binding Protein