Evidence that fibroblast growth factors 1 and 4 participate in regulation of cardiogenesis.
Previous studies in this laboratory have indicated that the early embryonic chick heart depends on fibroblast growth factor-2 (FGF-2; bFGF), sequentially utilized in paracrine and autocrine fashion, for its growth and development (Sugi and Lough, [1995] Dev. Biol. 168-567-574). This view emanated from immunohistochemical detection of FGF-like antigens in endoderm cells at stage 6, and later in the early myocardium at stage 9+ (Parlow et al. [1991] Dev. Biol. 146:139-147). To identify other members of the FGF family that are expressed by these cells, we have used peptide-generated antisera that specifically recognize FGFs 1 and 4. Like FGF-2, FGFs 1 and 4 were exclusively detected in the endoderm at stage 5+ and later in the myocardium, appearing as punctate cytoplasmic deposits. However, whereas FGF-2 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 in parallel with reduced myocardial cell proliferation. To determine these isoproteins' ability to facilitate the completion of terminal cardiac myocyte differentiation, stage 5+ precardiac mesoderm was cultured in defined medium with purified FGFs. Like FGF-2, as little as 5-10 ng/ml FGF-1 or FGF-4 supported the proliferation and differentiation of precardiac myoblasts, resulting in the formation of a vesicle containing an adherent multilayer of synchronously contractile cells. Evidence that this represented FGF receptor-mediated signaling rather than a nonspecific effect of exogenous FGF was indicated by the ability of sodium chlorate to inhibit FGF-mediated cardiogenesis. These findings are consistent with the hypothesis that, like FGF-2, FGFs 1 and 4 participate in the regulation of early heart development via paracrine and autocrine mechanisms.
Zhu
X
X
Department of Cellular Biology and Anatomy, Medical College of Wisconsin, Milwaukee 53226, USA.
Sasse
J
J
McAllister
D
D
Lough
J
J
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002704:Chlorates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004707:Endoderm / Q000737:chemistry; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism* / Q000494:pharmacology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000494:pharmacology; D007150:Immunohistochemistry; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000737:chemistry*; D011509:Proteoglycans / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000494:pharmacology; D014018:Tissue Distribution
D002704:Chlorates; D016220:Fibroblast Growth Factor 1; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; C032706:sodium chlorate