Multiple phases of myogenesis have been observed in all species. For example, in mammals, embryonic myogenesis is followed by fetal myogenesis, then neonatal myogenesis, finally myogenic repair. Although the basic transcriptional machinery for these different phases of myogenesis is similar and reasonably well understood, very little is known about the basic developmental biology of these different myogenic periods. In particular, it is not clear if there is a direct, lineal relationship between cells that underlie these different epochs. Is there one type of myogenic precursor that sequentially produces different types of muscle, or are there many types of precursors? Do the same signals regulate cell fate choices at each stage? Can we learn something relevant to stem cell biology by studying these different phases of muscle patterning? This application seeks to answer these long term questions, using the powerful combination of cellular embryology and genetics possible in the zebrafish. Inspired by lineage experiments, the earliest slow muscle precursors were proposed to be induced by Hedgehog signaling. After these embryonic slow muscle fibers develop, there are one or more phases of myogenesis in zebrafish, and the later, post-embryonic phase of myogenesis is only partially regulated by Hedgehog signaling. This application aims to use single-cell injections of lineage tracers to identify the precursors to this post-embryonic muscle growth. It also aims to characterize the role of Hedgehog signaling in post-embryonic myogenesis, using a combination of genetics, pharmacology, and experimental embryology. This research will answer questions of fundamental importance to the understanding of how cells develop into muscle fibers. This information is critical to understanding muscle diseases including heart disease and muscular dystrophy. When the signals regulating myogenesis are understood, it will be possible to guide stem cells towards a myogenic fate, to design therapies for devastating human diseases.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD037509-10
Application #
8080881
Study Section
Skeletal Muscle and Exercise Physiology Study Section (SMEP)
Program Officer
Javois, Lorette Claire
Project Start
1999-04-01
Project End
2013-04-30
Budget Start
2011-05-01
Budget End
2013-04-30
Support Year
10
Fiscal Year
2011
Total Cost
$252,393
Indirect Cost
Name
Wesleyan University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
145683954
City
Middletown
State
CT
Country
United States
Zip Code
06459
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