A ROLE FOR BONE MORPHOGENETIC PROTEINS IN THE INDUCTION OF CARDIAC MYOGENESIS

Little is known about the molecular mechanisms that govern heart speci fication in vertebrates. Here we demonstrate that bone morphogenetic p rotein (BMP) signaling plays a central role in the induction of cardia c myogenesis in the chick embryo. At the time when chick precardiac ce lls become committed to the cardiac muscle lineage, they are in contac t with tissues expressing BMP-2 BMP-4, and BMP-7. Application of BMP-2 -soaked beads in vivo elicits ectopic expression of the cardiac transc ription factors CNkx-2.5 and GATA-4. Furthermore, administration of so luble BMP-2 or BMP-4 to explant cultures induces full cardiac differen tiation in stage 5 to 7 anterior medial mesoderm, a tissue that is nor mally not cardiogenic. The competence to undergo cardiogenesis in resp onse to BMPs is restricted to mesoderm located in the anterior regions of gastrula- to neurula-stage embryos. The secreted protein noggin, w hich binds to BMPs and antagonizes BMP activity, completely inhibits d ifferentiation of the precardiac mesoderm, indicating that BMP activit y is required for myocardial differentiation in this tissue. Together, these data imply that a cardiogenic field exists in the anterior meso derm and that localized expression of BMPs selects which cells within this field enter the cardiac myocyte lineage.