We plan to study the cellular and molecular mechanisms involved in the differentiation of skeletal muscle. The function and regulation of expression of the muscle-specific membrane protein, H36, will be studied. This protein is a marker of the development of cells at distinct stages in the myogenic lineage. It also distinguishes primary (H36-) from secondary (H364+) myoblasts. H36 cDNA has been cloned: its complete nucleotide and amino acid sequences will determined. Genomic clones will be isolated and the mechanisms by which expression of H36 is regulated at different stages of myogenic development will be studied. We will determine whether the regulatory genes, MyoD1, myogenin, Myf5, Myf6 and Mrf4, can promote expression of H36 in cells at different stages of the myogenic lineage. The functions of H36 in myogenesis will be determined by transfection of the H36 gene into specific H36- developmental mutants and other appropriate cells, by using antisense oligonucleotides to inhibit its synthesis, and by blocking H36 function with monoclonal antibodies. Functional domains in the molecule will be identified by mutagenesis analysis. We will determine whether H36 and other membrane proteins known to be involved in myoblast interactions are involved in the molecular discrimination between primary and secondary myoblasts that underlies their autonomous development. These studies will resolve the functions and mechanisms that regulate H36 expression during early and terminal myogenesis and the mechanisms by which primary and secondary myoblasts interact and discriminate one another. This infommtion is essential to the fundamental understanding of cell interactions and skeletal muscle development that are needed to develop rational approaches to the selective repair and replacement of primary and secondary muscle fibers.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM028842-10A1
Application #
3276196
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1980-08-01
Project End
1995-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
10
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Hodges, B L; Hayashi, Y K; Nonaka, I et al. (1997) Altered expression of the alpha7beta1 integrin in human and murine muscular dystrophies. J Cell Sci 110 ( Pt 22):2873-81
Crawley, S; Farrell, E M; Wang, W et al. (1997) The alpha7beta1 integrin mediates adhesion and migration of skeletal myoblasts on laminin. Exp Cell Res 235:274-86
Wang, W; Wu, W; Desai, T et al. (1995) Localization of the alpha 7 integrin gene (ITGA7) on human chromosome 12q13: clustering of integrin and Hox genes implies parallel evolution of these gene families. Genomics 26:568-70
Gu, M; Wang, W; Song, W K et al. (1994) Selective modulation of the interaction of alpha 7 beta 1 integrin with fibronectin and laminin by L-14 lectin during skeletal muscle differentiation. J Cell Sci 107 ( Pt 1):175-81
Haider, S R; Wang, W; Kaufman, S J (1994) SV40 T antigen inhibits expression of MyoD and myogenin, up-regulates Myf-5, but does not affect early expression of desmin or alpha 7 integrin during muscle development. Exp Cell Res 210:278-86
Song, W K; Wang, W; Sato, H et al. (1993) Expression of alpha 7 integrin cytoplasmic domains during skeletal muscle development: alternate forms, conformational change, and homologies with serine/threonine kinases and tyrosine phosphatases. J Cell Sci 106 ( Pt 4):1139-52
George-Weinstein, M; Foster, R F; Gerhart, J V et al. (1993) In vitro and in vivo expression of alpha 7 integrin and desmin define the primary and secondary myogenic lineages. Dev Biol 156:209-29
Song, W K; Wang, W; Foster, R F et al. (1992) H36-alpha 7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis. J Cell Biol 117:643-57
Kaufman, S J; George-Weinstein, M; Foster, R F (1991) In vitro development of precursor cells in the myogenic lineage. Dev Biol 146:228-38
Kaufman, S J; Bielser, D; Foster, R F (1990) Localization of anti-clathrin antibody in the sarcomere and sensitivity of myofibril structure to chloroquine suggest a role for clathrin in myofibril assembly. Exp Cell Res 191:227-38

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