Retinoic acid can block differentiation of the myocardium after heart specification.

While a number of transcription factors that are likely to play a role in cardiac differentiation have recently been described, the signals that lead to the expression of these factors remains poorly understood. Here we report that exposure of Xenopus embryos to continuous low levels of all-trans retinoic acid (RA), starting at the time of neural fold closure, blocks expression of myocardial differentiation markers. The development of the remainder of the embryo is relatively normal, suggesting that retinoic acid can act rather specifically on myocardial precursors. Indeed, the pattern of endocardial gene expression appears to remain unaffected by RA treatment. Although RA blocks myocardial gene expression, a superficially normal heart tube forms. The heart tube, however, fails to loop during subsequent development and never forms beating tissue. The effect of RA treatment on expression of myocardial genes is developmental stage dependent, since no influence is observed after myocardial differentiation has commenced. These data indicate that a vital component of the myocardial determination pathway is sensitive to retinoid signaling.