The in Vivo Expression of the FGF Receptor FREK mRNA in Avian Myoblasts Suggests a Role in Muscle Growth and Differentiation

Abstract

Muscle growth during embryogenesis is the result of a balance between the proliferation of myoblasts and their differentiation into mature, contractile fibers. Fibroblast growth factors (FGFs) are potent stimulators of myoblast proliferation and inhibitors of myoblast differentiationin vitro.However, it is not clear at present if FGFs and their receptors regulate this processin vivo,partially because no FGF receptor was known to be expressed by myoblasts during embryogenesis. In this study, we have used quail/chick grafting and BrdU labeling techniques to demonstrate that a recently cloned avian FGF receptor, FREK, is expressed by replicating skeletal muscle myoblasts, while differentiated muscle cells no longer express this receptor. In the limb, muscle progenitors originating from the somite start expressing FREK at 3 days of development (E3). FREK expression in the limb myoblasts follows that of Pax-3 and Pax-7, but precedes that of MyoD. Since MyoD expression signals the onset of terminal differentiation, this demonstrates that FREK is expressed in muscle progenitors prior to overt muscle differentiation. A more complex situation is observed in the trunk region, where a first wave of MyoD-positive myocytes, which are postmitotic and never express FREK, appear in the early myotomal compartment of the somite. Slightly later, at E2.5, FREK-positive myoblasts migrate into the myotome as a second wave of muscle progenitors, 15 hr after the first MyoD-positive cells. FREK's expression by myoblasts arising at all stages of myogenesis indicates that this growth factor receptor represents one of the earliest molecular markers for this cell population. FREK's prominent expression during muscle differentiation sets it apart from other FGF receptors and suggests that this molecule plays an important role during muscle growth and differentiation.