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Published April 1999 | public
Journal Article

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-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.

Additional Information

© 1999 by Cell Press. Under an Elsevier user license. Received 3 September 1998, Revised 23 February 1999, Available online 22 September 2000. We acknowledge Andrew Groves for initial studies of TH induction; Christo Goridis for support and input; members of the Anderson lab for helpful discussions; L. Wang, S. Padilla, and L. Dinh for technical support; G. Mosconi for lab management; L. Sommer for the GFP construct; and Alice Paquette for a critical reading of the manuscript. This work was supported in part by the Association pour la Recherche sur le Cancer to J.-F. B. D. J. A. is an Investigator of the Howard Hughes Medical Institute.

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