Activin-A and FGF-2 mimic the inductive effects of anterior endoderm on terminal cardiac myogenesis in vitro.

We recently reported that the differentiation of cultured embryonic precardiac myocytes is specifically promoted by anterior lateral plate endoderm from Hamburger-Hamilton stage 6 chick embryos. Polypeptide growth factors are probable mediators of cardiogenesis during embryonic development. It was previously noted that activin-A is a major secretory product of endoderm cultured from chicken embryos. Also, fibroblast growth factor-like proteins are present in anterior endoderm of stage 6 chick embryos. Therefore, we have examined the cardiogenic effects of these growth factors on cultured precardiac mesoderm cells explanted from stage 6 embryos. Similar to the effects of anterior endoderm, low concentrations of activin-A, FGF-2 (bFGF), or insulin significantly increased the incidence of explants that exhibited synchronous contractions and expressed cardiac alpha-actin mRNA. By contrast, explants treated with transferrin, bovine serum albumin, or nerve growth factor never contracted and contained only cytoplasmic beta-actin transcripts. These results provide additional evidence that endoderm-secreted activin-A, FGF-2, and perhaps insulin participate in regulating terminal cardiac differentiation in the embryo.