Developmentally regulated expression and localization of fibroblast growth factor receptors in the human muscle

• Published in: Developmental dynamics 1998-04, Vol.211 (4), p.362-373
• Main Authors: Sogos, Valeria, Balaci, Lenuta, Ennas, Maria Grazia, Dell'Era, Patrizia, Presta, Marco, Gremo, Fulvia
• Format: Article
• Language: English
• Subjects: Adult; Blotting, Northern; Cell Nucleus - metabolism; Cells, Cultured; development; fibroblast growth factors; Heparan Sulfate Proteoglycans; Heparitin Sulfate - metabolism; human fetus; Humans; Immunohistochemistry; Membrane Glycoproteins - metabolism; Microscopy, Confocal; muscle; muscle proteins; Muscle, Skeletal - embryology; Muscle, Skeletal - metabolism; Myosins - metabolism; Protein-Tyrosine Kinases; Proteoglycans - metabolism; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 3; Receptor, Fibroblast Growth Factor, Type 4; receptors; Receptors, Fibroblast Growth Factor - metabolism; RNA, Messenger - analysis; Syndecan-1; Syndecans; Time Factors
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/(SICI)1097-0177(199804)211:4<362::AID-AJA7>3.0.CO;2-F

Fibroblast growth factors (FGFs) are believed to play a key role in tissue differentiation and maturation. Thus, the expression of the four members of the high‐affinity tyrosine kinase FGF receptor family (FGFRs) and of the low‐affinity heparan sulphate proteoglycan binding sites, syndecan‐1 and perlecan, was studied in the human skeletal muscle during development. Northern blot analysis demonstrated a developmentally regulated expression of the mRNAs for FGFR‐1, FGFR‐3, FGFR‐4, whereas only traces of FGFR‐2 mRNA were found. Each receptor type had a different developmental pattern, suggesting an independent regulation. Signal for FGFR‐3 was retained only in the adult muscle. Among the low‐affinity FGF binding sites, perlecan was absent, whereas RNA transcript for syndecan‐1 peaked at week 13 of gestation, after which a significant 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 later 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 all, muscle fibers, and FGFR‐4 maintained an association with plasma membrane. In adult tissue, weak positivity for FGFR‐3 and FGFR‐4 was observed in the connective tissue only.  When immunocytochemistry was performed 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 expression and cell distribution of FGFRs play a role during muscle maturation. Dev. Dyn. 1998;211:362–373. © 1998 Wiley‐Liss, Inc.