SCUBE3 (signal peptide-CUB-EGF domain-containing protein 3) modulates fibroblast growth factor signaling during fast muscle development.
SCUBE3 (signal peptide CUB-EGF-like domain-containing protein 3) belongs to a newly identified secreted and cell membrane-associated SCUBE family, which is evolutionarily conserved in vertebrates. Scube3 is predominantly expressed in a variety of developing tissues in mice such as somites, neural tubes, and limb buds. However, its function during development remains unclear. In this study, we first showed that knockdown of SCUBE3 in C2C12 myoblasts inhibited FGF receptor 4 expression and FGF signaling, thus resulting in reduced myogenic differentiation. Furthermore, knockdown of zebrafish scube3 by antisense morpholino oligonucleotides specifically suppressed the expression of the myogenic marker myod1 within the lateral fast muscle precursors, whereas its expression in the adaxial slow muscle precursors was largely unaffected. Consistent with these findings, immunofluorescent staining of fast but not slow muscle myosin was markedly decreased in scube3 morphants. Further genetic studies identified fgf8 as a key regulator in scube3-mediated fast muscle differentiation in zebrafish. Biochemical and molecular analysis showed that SCUBE3 acts as a FGF co-receptor to augment FGF8 signaling. Scube3 may be a critical upstream regulator of fast fiber myogenesis by modulating fgf8 signaling during zebrafish embryogenesis.
From the Institute of Biomedical Sciences and the, Academia Sinica, Taipei 11529, Taiwan, the Molecular Medicine Program, Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, the Institute of Biochemistry and Molecular Biology and.
Cheng-Fen
CF
Tu
From the Institute of Biomedical Sciences and the, Academia Sinica, Taipei 11529, Taiwan.
Ku-Chi
KC
Tsao
the Department of Life Science, National Taiwan University, Taipei 10617, Taiwan.
Shyh-Jye
SJ
Lee
From the Institute of Biomedical Sciences and the, Academia Sinica, Taipei 11529, Taiwan, the Molecular Medicine Program, Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, the Institute of Biochemistry and Molecular Biology and the Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan, rbyang@ibms.sinica.edu.tw.
Ruey-Bing
RB
Yang
D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D024510:Muscle Development; D017570:MyoD Protein / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D002135:Calcium-Binding Proteins; C496456:FGF8 protein, human; C496457:Fgf8 protein, mouse; D006023:Glycoproteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C493800:SCUBE3 protein, human; C000592362:SCUBE3 protein, zebrafish; C493801:Scube3 protein, mouse; D029961:Zebrafish Proteins; D051524:Fibroblast Growth Factor 8; C496371:FGFR4 protein, human; C496372:Fgfr4 protein, mouse; D051499:Receptor, Fibroblast Growth Factor, Type 4
Cell Differentiation; Fast Muscle; Fibroblast Growth Factor (FGF); Fibroblast Growth Factor Receptor (FGFR); Myogenesis; Zebrafish; scube3