In this interesting grant proposal, Dr. Abmayr intends to study an aspect of muscle cell formation that is currently poorly understood. Using Drosophila as a model system, she intends to investigate the mechanism by which fusion of myoblasts is controlled and regulated. Muscle cells are one of the few cells that can form multinucleate syncitia. While other aspects of muscle cell differentiation have been studied intensely, little is known about the mechanism of myoblast fusion. Muscle fibers can attain precise sizes in accordance with their location suggesting that there is a highly regulated decision-making process associated with patterning. In Drosophila, there is ample evidence that those decisions are made quite early in myoblast determination. In this proposal, it is intended to take advantage of a combined genetic and molecular approach to examine myoblast fusion. In particular, the cloning of two novel genes called sticks and stones (sns) and myoblast city (mbc) will be attempted. Mutant phenotypes associated with these genes include a dramatic decrease in differentiated muscle fibers and, importantly, a large number of unfused myoblasts. After the cloning of these genes their sequences will be determined, critical protein encoding and promoter regulatory regions will be mapped. In addition, vertebrate homologues will be isolated, expecting that these genes, like many other developmental genes, are highly conserved in evolution. It is therefore possible that this analysis will also lead to the identification of genes that are crucial for vertebrate muscle cell fusion.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Biological Sciences 2 (BIOL)
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Lymn, Richard W
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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Haralalka, Shruti; Abmayr, Susan M (2015) Tracing myoblast fusion in Drosophila embryos by fluorescent actin probes. Methods Mol Biol 1313:149-64
Kumar, Ram P; Dobi, Krista C; Baylies, Mary K et al. (2015) Muscle cell fate choice requires the T-box transcription factor midline in Drosophila. Genetics 199:777-91
Haralalka, Shruti; Shelton, Claude; Cartwright, Heather N et al. (2014) Live imaging provides new insights on dynamic F-actin filopodia and differential endocytosis during myoblast fusion in Drosophila. PLoS One 9:e114126
Kaipa, Balasankara Reddy; Shao, Huanjie; Schäfer, Gritt et al. (2013) Dock mediates Scar- and WASp-dependent actin polymerization through interaction with cell adhesion molecules in founder cells and fusion-competent myoblasts. J Cell Sci 126:360-72
Haralalka, Shruti; Cartwright, Heather N; Abmayr, Susan M (2012) Recent advances in imaging embryonic myoblast fusion in Drosophila. Methods 56:55-62
Haralalka, Shruti; Shelton, Claude; Cartwright, Heather N et al. (2011) Asymmetric Mbc, active Rac1 and F-actin foci in the fusion-competent myoblasts during myoblast fusion in Drosophila. Development 138:1551-62
Liu, Ze Cindy; Geisbrecht, Erika R (2011) Moleskin is essential for the formation of the myotendinous junction in Drosophila. Dev Biol 359:176-89
Haralalka, Shruti; Abmayr, Susan M (2010) Myoblast fusion in Drosophila. Exp Cell Res 316:3007-13
Shelton, Claude; Kocherlakota, Kiranmai S; Zhuang, Shufei et al. (2009) The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts. Development 136:1159-68
Geisbrecht, Erika R; Haralalka, Shruti; Swanson, Selene K et al. (2008) Drosophila ELMO/CED-12 interacts with Myoblast city to direct myoblast fusion and ommatidial organization. Dev Biol 314:137-49

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