Retinoic acid influences Phox2 expression of cardiac ganglionic cells in the developing rat heart.

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. 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. Phox2b expression remained unchanged in the differentiated phase of cardiac ganglionic cell development after RA treatment, whereas the population of cells expressing Phox2a, PGP9.5 and S-100 was diminished. 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.