13 - Retinoids in Heart Development

Abstract

Clues to the function of retinoids in heart development came initially from studies of the effects of vitamin A-deficient diets on the pups of pregnant rats. Two general experimental strategies have been employed in these efforts. Retinoid-deficient diets (or loss-of-function genetic manipulation of retinoid receptors) cause heart defects because of failures in endogenous retinoid-dependent developmental processes. Alternatively, ectopic administration of an excess of retinoids results in defects that reflect the competence of the developing heart to respond to retinoids, although this response might not necessarily occur in normally developing embryos or might not occur to as great an extent. It is found that retinoids have a broad role in directing normal cardiovascular morphogenesis, and that the developing heart is extremely sensitive to perturbation (in either direction) of retinoid signaling. Previously, a popular model held that retinoic acid (RA) worked by establishing positional identity within a developmental field, such as the limb bud or in principle the heart. Recent analyses are far more supportive of a conceptualization of RA acting in multiple independent events during the course of heart development, even though these events are closely linked in space and time.