FGF 1 Promotes Commitment of Epiblast to Cardiac Lineage at Early Stage of Development

The differentiation of cardiomyocytes has been studied intensively. However, it remains unclear regarding the first commitment of cardiogenic progenitor cells in the primitive streak in the early gastrula. We demonstrated that fibroblast growth factor 1 (FGF 1) may play significant roles in the specification of heart primordium, employing a pluripotent embryonal carcinoma cell, P19, culture system. FGF 1 was expressed markedly from day 2 to 3, corresponding to the early primitive streak stage of the embryo, in cultures with 10^<-12>M retinoic acid (RA), in which the cells finally differentiated into cardiac myocytes. Addition of FGF 1 to cultures containing 10^<-8>M RA, a condition inducing skeletal muscle differentiation, resulted in induction of alpha-cardiac myosin heavy chain gene expression with up-regulation of FGF receptor type 1 (FGFR 1), bone morphogenic protein-4 (BMP 4) and GATA 4. Experiments with anti-FGFR 1 antibody showed that the signal transduction of FGF 1 was at least partially mediated via FGFR 1. Furthermore, FGF 1 protein was detected in rat embryos at the early primitive streak stage. FGF 1 stained strongly in the hypoblast adjacent to mid-posterior part of the primitive streak where the cardiac primordium is known to ingress. Taken together, the findings of our study imply that epiblast cells of the early gastrula receive FGF 1 signals from the hypoblast adjacent to the posterior primitive streak for the first commitment of cardiac precursor cells