Sequential programs of retinoic acid synthesis in the myocardial and epicardial layers of the developing avian heart

Endogenous patterns of retinoic acid (RA) signaling in avian cardiac morpho genesis were characterized by localized expression of a key RA-synthetic en zyme, RALDH2, which displayed a biphasic pattern during heart development. RALDH2 immunoreactivity was initially apparent posterior to Hensen's node o f stage 5-6 embryos and subsequently in somites and unsegmented paraxial an d lateral plate mesoderm overlapping atrial precursors in the cardiogenic p late of stage 9- embryos. Initial RALDH2 synthesis in the posterior myocard ium coincided with activation of the AMHC1 gene, a RA-responsive marker of inflow heart segments. A wave of RALDH2 synthesis then swept the myocardium in a posterior-to-anterior direction, reaching the outflow tract by stage 13, then fading from the myocardial layer. The second phase of RALDH2 expre ssion, initiated at stage 18 in the proepicardial organ, persisted in mi,or atory epicardial cells that completely enveloped the heart by stage 24. Ear ly restriction of RALDH2 expression to the posterior cardiogenic plate, ove rlapping RA-inducible gene activation, provides evidence for commitment of posterior avian heart segments by localized production of RA, whereas subse quent RALDH2 expression exclusively in the migratory epicardium suggests a role for the morphogen in ventricular expansion and morphogenesis of underl ying myocardial tissues. (C) 2000 Academic Press.