DEVELOPMENTALLY-REGULATED EXPRESSION AND LOCALIZATION OF FIBROBLAST GROWTH-FACTOR RECEPTORS IN THE HUMAN MUSCLE

Fibroblast growth factors (FGFs) are believed to play a key role in ti ssue differentiation and maturation, Thus, the expression of the four members of the high-affinity tyrosine kinase FGF receptor family (FGFR s) and of the low-affinity heparan sulphate proteoglycan binding sites , syndecan-1 and perlecan, was studied in the human skeletal muscle du ring development. Northern blot analysis demonstrated a developmentall y regulated expression of the mRNAs for FGFR-1, FGFR-3, FGFR-4, wherea s only traces of FGFR-2 mRNA were found, Each receptor type had a diff erent developmental pattern, suggesting an independent regulation, Sig nal for FGFR-3 was retained only in the adult muscle, Among the low-af finity FGF binding sites, perlecan was absent, whereas RNA transcript for syndecan-1 peaked at week 13 of gestation, after which a significa nt decrease was observed. Immunohistochemistry for FGFRs revealed that their localization changed with muscle maturation, At early embryonic stages, FGFR-3 and FGFR-4 had a scattered distribution in the tissue, and FGFR-1 was found on myotube and myofiber plasma membranes, At lat er stages, FGFR-1 positivity decreased and was found in a few areas of the muscle, FGFR-3 was concentrated in the nuclei of some, but not al l, muscle fibers, and FGFR-4 maintained an association with plasma mem brane, In adult tissue, weak positivity for FGFR-3 and FGFR-4 was obse rved in the connective tissue only, When immunocytochemistry was perfo rmed on human fetal myoblasts in culture, confocal microscope analysis revealed a nonhomogeneous cell membrane distribution of FGFRs. Taken together, the data strongly suggest that developmentally regulated exp ression and cell distribution of FGFRs play a role during muscle matur ation. (C) 1998 Wiley-Liss, Inc.