Disease relevance of Phox2a

• To test this hypothesis, we examined whether the homeodomain transcription factors Phox2a/2b play a role in activity-dependent expression of the dopaminergic phenotype using petrosal ganglion (PG) sensory neurons as a model [1].

High impact information on Phox2a

• In collaboration with cAMP, Phox2a can induce expression of TH but not of DBH or of panneuronal genes [2].
• Age-related changes in the gene expression of the transcription factors, Phox2a and 2b, and two marker proteins, norepinephrine transporter (NET) and dopamine beta-hydroxylase (DBH), of noradrenergic neurons were characterized in the locus coeruleus (LC) and adrenal glands using in situ hybridization [3].
• A direct role of the homeodomain proteins Phox2a/2b in noradrenaline neurotransmitter identity determination [4].
• Single point mutations in the homeodomain of Phox2a resulted in a failure to transactivate the DBH promoter in vitro and resulted in the loss of NA neurons in vivo [4].
• Mutations in three or four, but not one or two, of the binding sites completely abolished activation of the DBH promoter by Phox2a or 2b, while the conversion of PBD3 to a consensus motif (ATTA) improved the DBH promoter activity by > 10-fold [4].

Anatomical context of Phox2a

• These results suggest that RA disrupts the differentiation of cardiac neural crest cells into ganglionic cells destined to contribute to the parasympathetic innervation of the heart, by regulating the expression of Phox2a and Phox2b [5].

Associations of Phox2a with chemical compounds

• The timing of Phox2a/2b expression is precisely correlated with the ability of PG neurons to express the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), in response to depolarizing stimuli [1].
• We have studied the expression of the homeodomain transcriptional neuronal regulators Phox2a, Phox2b and the non-neuronal Schwann cell response using the marker S-100 in the differentiating phase of cardiac ganglionic cells in rat embryos following exogenous retinoic acid (RA) treatment of pregnant dams [5].

Other interactions of Phox2a

• In control embryos, the expression of Phox2b (E11) preceded that of Phox2a, which, along with the terminal neuronal differentiation marker PGP9.5, was expressed from E12 onwards [5].

References