[PDF][PDF] Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells

L Lo, X Morin, JF Brunet, DJ Anderson - Neuron, 1999 - cell.com
L Lo, X Morin, JF Brunet, DJ Anderson
Neuron, 1999cell.com
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-β hydroxylase (DBH) gene expression in these
cells. In collaboration with cAMP, Phox2a can induce expression of TH but not of DBH or of …
Abstract
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-β 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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