Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells.

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-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.

journal_name

Neuron

journal_title

Neuron

authors

Lo L,Morin X,Brunet JF,Anderson DJ

doi

10.1016/s0896-6273(00)80729-1

subject

Has Abstract

pub_date

1999-04-01 00:00:00

pages

693-705

issue

4

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(00)80729-1

journal_volume

22

pub_type

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