A NEW AVIAN FIBROBLAST GROWTH-FACTOR RECEPTOR IN MYOGENIC AND CHONDROGENIC CELL-DIFFERENTIATION

We studied the expression of FREK (fibroblast growth factor receptor-l ike embryonic kinase), a new receptor recently cloned from quail embry o, during the differentiation of skeletal muscle satellite cells and e piphyseal growth-plate chondrocytes. Although FREK mRNA was expressed in both cell types, satellite cells expressed higher levels of this mR NA than chondrocytes. FREK gene expression was found to be modulated b y b-FGF in a biphasic manner: low concentrations increased expression, whereas high concentrations attenuated it. In both cell cultures, the levels of FREK mRNA declined during terminal differentiation. Moreove r, retinoic acid (RA), which induces skeletal muscle satellite cells t o differentiate, also caused a reduction in FREK gene expression in th ese cells. Induction of chondrocyte differentiation with ascorbic acid was monitored by a decrease in collagen type II gene expression and a n increase in alkaline phosphatase activity. Satellite cell differenti ation was marked by morphological changes as well as by increased sarc omeric myogenin content and creatine kinase activity and changes in th e expression of the regulatory muscle-specific genes, MyoD and myogeni n. DNA synthesis in both cell types was stimulated by b-FGF. However, in satellite cells, the response was bell-shaped, peaking at 1 ng/ml b -FGF, whereas in chondrocytes, higher levels of b-FGF were needed. b-F GF-dependent DNA synthesis in satellite cells was decreased by RA at c oncentrations over 10(-7) M. The observed correlation between the leve l of FREK gene expression and various stages of differentiation, its m odulation by b-FGF and RA, as well as the correlation between FREK gen e expression and the physiological response to b-FGF, suggest that thi s specific FGF receptor plays an important role in muscle and cartilag e cell differentiation. Press,Inc. (C) 1994 Academic Press, Inc.