“Wings of the heart”: messages that direct heart mesenchyme into fibrogenic lineages

The mesenchymal cells of the embryonic heart that secrete periostin normally differentiate into fibroblasts of the valves and cardiac skeleton. However, there is evidence that these cells can be reprogrammed or redirected into other mesodermal lineages when a gene, periostin, is genetically deleted or silenced. To verify if heart mesenchyme is truly multipotential we initiated chick/quail chimeric studies to determine the fate of heart prevalvular mesenchyme when placed into a wing bud setting. Depending upon the age and placement of heart grafts, results indicated that in wing bud environment (or in defined media with little or no periostin) valve progenitor mesenchyme differentiated into chondrogenic, myogenic and even hemangiogenic lineages. In vivo and in vitro rescue and gene manipulation experiments (1) confirmed that periostin acting through integrin linked signaling pathways could induce target progenitor cells to become heart fibroblasts and (2) that two downstream targets, notch 1 and filamin A, mediated the effects of periostin signaling upon cardiac mesenchyme differentiation. Supported by NHLBI 33756, NSF FIBR Grant and Leducq Mitral Grant