Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells.
We have investigated the specification of noradrenergic neurotransmitter identity in neural crest stem cells (NCSCs). Retroviral expression of both wild-type and dominant-negative forms of the paired homeodomain transcription factor Phox2a indicates a crucial and direct role for this protein (and/or the closely related Phox2b) in the regulation of endogenous tyrosine hydroxylase (TH) and dopamine-beta hydroxylase (DBH) gene expression in these cells. In collaboration with cAMP, Phox2a can induce expression of TH but not of DBH or of panneuronal genes. Phox2 proteins are, moreover, necessary for the induction of both TH and DBH by bone morphogenetic protein 2 (BMP2) (which induces Phox2a/b) and forskolin. They are also necessary for neuronal differentiation. These data suggest that Phox2a/b coordinates the specification of neurotransmitter identity and neuronal fate by cooperating environmental signals in sympathetic neuroblasts.
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Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.
Morin
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Brunet
J F
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Anderson
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DJ
D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005799:Genes, Dominant; D018398:Homeodomain Proteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D051381:Rats; D013234:Stem Cells / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D018398:Homeodomain Proteins; C109220:NBPhox protein; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C100935:Phox2a protein, rat; D014157:Transcription Factors; D005576:Colforsin; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase