EVIDENCE THAT FIBROBLAST GROWTH-FACTOR-1 AND GROWTH-FACTOR-4 PARTICIPATE IN REGULATION OF CARDIOGENESIS

Previous studies in this laboratory have indicated that the early embr yonic chick heart depends on fibroblast growth factor-a (FGF-S; bFGF), sequentially utilized in paracrine and autocrine fashion, for its gro wth and development (Sugi and Lough, [1995] Dev. Biol. 168:567-574). T his view emanated from immunohistochemical detection of FGF-like antig ens in endoderm cells at stage 6, and later in the early myocardium at stage 9+ (Parlow ct al. [1991] Dev. Biol. 146:139-147). To identify o ther members of the FGF family that are expressed by these cells, we h ave used peptide-generated antisera that specifically recognize FGFs 1 and 4. Like FGF-2, FGFs 1 and 4 were exclusively detected in the endo derm at stage 5+ and later in the myocardium, appearing as punctate cy toplasmic deposits. However, whereas FGF-S is first detected at stage 9+, FGFs 1 and 4 did not appear until stages 11 and 15, respectively. Expression of all FGFs peaked at stages 18-24, decreasing thereafter i n parallel with reduced myocardial cell proliferation. To determine th ese isoproteins' ability to facilitate the completion of terminal card iac myocyte differentiation, stage 5+ precardiac mesoderm was cultured in defined medium with purified FGFs. Like FGF-2, as little as 5-10 n g/ml FGF-1 or FGF-4 supported the proliferation and differentiation of precardiac myoblasts, resulting in the formation of a vesicle contain ing an adherent multilayer of synchronously contractile cells. Evidenc e that this represented FGF receptor-mediated signaling rather than a nonspecific effect of exogenous FGF was indicated by the ability of so dium chlorate to inhibit FGF-mediated cardiogenesis. These findings ar e consistent with the hypothesis that, like FGF-S, FGFs 1 and 4 partic ipate in the regulation of early heart development via paracrine and a utocrine mechanisms. (C) 1996 Wiley-Liss, Inc.