Role of fibroblast growth factor signaling during proepicardium formation in the chick embryo.

The proepicardium forms at the venous pole of the embryonic heart and gives rise to several cell types of the mature heart. We investigated the role of fibroblast growth factors (FGFs) during proepicardium formation in the chick embryo. Several FGF ligands (Fgf2, Fgf10, and Fgf12) and receptors (Fgfr1, Fgfr2, and Fgfr4) are expressed in the proepicardium. Experimental modulation of FGF signaling in explant cultures affected cell proliferation and survival. In contrast, expression of Tbx18, Wt1, or Tbx5 were unaffected by FGF inhibition. In agreement with the explant data, villous outgrowth of the proepicardium was strongly impaired by FGF inhibition in vivo, however Tbx18 expression was maintained. These data suggest that during proepicardium formation, FGF ligands act as autocrine or paracrine growth factors to prevent apoptosis, maintain proliferation, and to promote villous outgrowth of the proepicardium. However, FGF is not involved in the induction or maintenance of proepicardium-specific marker gene expression.