Our aim is to define the mechanisms which control skeletal muscle fiber diversity. Human skeletal muscles function in locomotion and posture, and many myopathies affect one group of muscles over another. However relatively little is known of how genetically similar myoblasts contribute to muscles with distinct physiological phenotypes. Elucidating mechanisms that control tissue-specific development will be helpful in designing rational therapies for muscle-related diseases. This research will focus on the development of diversity in the muscles of Drosophila. The adult thorax contains two muscle types which are distinguishable morphologically, biochemically and in muscle protein isoform usage. To determine how distinct muscles arise we shall identify factors controlling the transcriptional regulation of two fiber-specific genes. We shall also determine the roles of signaling molecules in the generation of fiber diversity, by ectopically expressing particular signals and assaying the fiber types resulting. This will be used in combination with screens to identify loci which specify particular muscles. These findings will contribute to understanding how mesodermal cells are specified to give rise to diverse muscle types, and how different factors induce diversity in muscles. Extensive research has already proven that the mechanisms controlling myogenesis are highly conserved through evolution, therefore the identification of factors controlling muscle fiber diversity in Drosophila will be highly relevant to our understanding of myogenesis in vertebrates.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM061738-01A1
Application #
6331029
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Greenberg, Judith H
Project Start
2001-05-01
Project End
2006-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
1
Fiscal Year
2001
Total Cost
$224,000
Indirect Cost
Name
University of New Mexico
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Dohn, Tracy E; Cripps, Richard M (2018) Absence of the Drosophila jump muscle actin Act79B is compensated by up-regulation of Act88F. Dev Dyn 247:642-649
Chechenova, Maria B; Maes, Sara; Oas, Sandy T et al. (2017) Functional redundancy and nonredundancy between two Troponin C isoforms in Drosophila adult muscles. Mol Biol Cell 28:760-770
Lovato, TyAnna L; Cripps, Richard M (2017) High Heart: A Role for Calcineurin Signaling in Hypoxia-Influenced Cardiac Growth. Circ Cardiovasc Genet 10:
Adema, Coen M; Hillier, LaDeana W; Jones, Catherine S et al. (2017) Whole genome analysis of a schistosomiasis-transmitting freshwater snail. Nat Commun 8:15451
Lovato, TyAnna L; Cripps, Richard M (2016) Regulatory Networks that Direct the Development of Specialized Cell Types in the Drosophila Heart. J Cardiovasc Dev Dis 3:
Chechenova, Maria B; Maes, Sara; Cripps, Richard M (2015) Expression of the Troponin C at 41C Gene in Adult Drosophila Tubular Muscles Depends upon Both Positive and Negative Regulatory Inputs. PLoS One 10:e0144615
Elwell, Jennifer A; Lovato, TyAnna L; Adams, Melanie M et al. (2015) The myogenic repressor gene Holes in muscles is a direct transcriptional target of Twist and Tinman in the Drosophila embryonic mesoderm. Dev Biol 400:266-76
Lovato, TyAnna L; Sensibaugh, Cheryl A; Swingle, Kirstie L et al. (2015) The Drosophila Transcription Factors Tinman and Pannier Activate and Collaborate with Myocyte Enhancer Factor-2 to Promote Heart Cell Fate. PLoS One 10:e0132965
Brunetti, Tonya M; Fremin, Brayon J; Cripps, Richard M (2015) Identification of singles bar as a direct transcriptional target of Drosophila Myocyte enhancer factor-2 and a regulator of adult myoblast fusion. Dev Biol 401:299-309
Oas, Sandy T; Bryantsev, Anton L; Cripps, Richard M (2014) Arrest is a regulator of fiber-specific alternative splicing in the indirect flight muscles of Drosophila. J Cell Biol 206:895-908

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