Retinoids and Heart Development

Publisher Summary This chapter reviews the experimental evidence that has implicated retinoic acid in several events of cardiac development, from early specification and/or patterning of the cardiac field to the control of myocardial differentiation. A substantial amount of this data has been obtained through phenotypic studies performed on the VAD quail model, as well as in targeted mouse mutants for the various RARs and RXRs and the synthesizing enzyme RALDH2. In parallel, a battery of experimental approaches have been used in each of the vertebrate models for studying development, from zebrafish (which, interestingly, provided evidence that retinoic acid has been functioning in vertebrates prior to the appearance of the four-chambered heart) to mouse. Quite often, these studies have compared the effects of exposure to exogenous retinoic acid, either to the whole embryo or by local administration, to those of a pharmacological inhibition of endogenous signaling using synthetic RAR/RXR antagonists or inhibitors of retinoic acid synthesis. The major outcomes—and sometimes the discrepancies—obtained in various animal models and/or distinct experimental approaches are discussed hereafter.