RETINOIC ACID DIRECTS CARDIAC LATERALITY AND THE EXPRESSION OF EARLY MARKERS OF PRECARDIAC ASYMMETRY

Formation of the left/right body axis is a critical early step in embr yogenesis. The heart Loop is one of the first clearly recognizable mor phological asymmetries, and the molecular pathway which dictates this laterality is now beginning to be understood. We report here that the left and right precardiac fields of chick differ in their sensitivity to retinoic acid (RA); while RA applied to the right precardiac field at gastrulation randomizes heart looping, Left side treatment induces situs inversus only at high RA concentrations. We identified two extra cellular matrix proteins, the heart-specific lec tin-associated matrix protein-1 (hLAMP1) and the fibrillin-related protein recognized by th e antibody JB3, which are distributed asymmetrically within the precar diac fields at the head process stage. In normal embryos, JB3 expressi on is enhanced within the right precardiac held, and hLAMP-1 is enrich ed within the left. RA treatment predictably altered the expression of these proteins in a manner consistent with subsequent heart lateralit y: RA treatments which randomize heart loop direction also equalized o r reversed the left/right JB3 and hLAMP-1 distribution prior to heart tube fusion. The existence of asymmetrically expressed extracellular m atrix proteins within precardiac regions suggests that interactions be tween cardiocytes and their environment may contribute to heart latera lity determination and looping. (C) 1997 Academic Press.