Vertebrate skeletal muscles are composed of two major populations of cells, slow muscle cells and fast muscle cells. These cells with their specific functions and pattern of gene expression, have become a popular system for studying mechanisms that underlie determination of cell fate. Recent studies have demonstrated that slow and fast muscle is regulated by Hedgehog secreted by the notochord, and bone morphogenetic proteins (BMPs) secreted by ectoderm cells. Hedgehogs and BMPs impose their patterning activities on responsive cells via transcription factors, that in turn regulating differentiation programs in responsive cells. Many genetic studies have implicated Glis in transducing HH and BMP signals. Several members of the Gli family are expressed in somites of Xenopus, chick, mouse and zebrafish embryos. Recent genetic studies in zebrafish have shown that a mutation in Gli2 causes a defect in slow muscle formation. The investigators have recently isolated a full length Gli4 from zebrafish. Preliminary data have shown that Gli4 is strongly expressed in paraxial mesoderm and developing somites. They hypothesize that members of the Gli family of transcription factors regulate differentiation of slow and fast muscle cell lineages in zebrafish, and that the expression of individual Glis and their ability to activate or inhibit transcription of responsive genes is controlled by Hedgehogs and BMPs. The regulation of Gli activity may occur at transcriptional, translational and/or posttranslational level (proteolysis).
The specific aim of this proposal is to investigate the expression, function and regulation of Gli4 in the differentiation of muscle cells in zebrafish embryos. The long-term goal of this study is to elucidate the molecular mechanisms behind determination of muscle-specific cell fate during embryonic development.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Cell Development and Function Integrated Review Group (CDF)
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Greenberg, Judith H
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University of MD Biotechnology Institute
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Haga, Yutaka; Dominique 3rd, Vincent J; Du, Shao Jun (2009) Analyzing notochord segmentation and intervertebral disc formation using the twhh:gfp transgenic zebrafish model. Transgenic Res 18:669-83
Rotllant, Josep; Liu, Dong; Yan, Yin-Lin et al. (2008) Sparc (Osteonectin) functions in morphogenesis of the pharyngeal skeleton and inner ear. Matrix Biol 27:561-72
Du, Shao Jun; Rotllant, Josep; Tan, Xungang (2006) Muscle-specific expression of the smyd1 gene is controlled by its 5.3-kb promoter and 5'-flanking sequence in zebrafish embryos. Dev Dyn 235:3306-15
Tan, Xungang; Rotllant, Josep; Li, Huiqing et al. (2006) SmyD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos. Proc Natl Acad Sci U S A 103:2713-8
Vasta, Gerardo R; Ahmed, Hafiz; Du, Shao- J et al. (2004) Galectins in teleost fish: Zebrafish (Danio rerio) as a model species to address their biological roles in development and innate immunity. Glycoconj J 21:503-21
Ahmed, Hafiz; Du, Shao-J; O'Leary, Nuala et al. (2004) Biochemical and molecular characterization of galectins from zebrafish (Danio rerio): notochord-specific expression of a prototype galectin during early embryogenesis. Glycobiology 14:219-32
Xu, Cheng; Wu, Gang; Zohar, Yonathan et al. (2003) Analysis of myostatin gene structure, expression and function in zebrafish. J Exp Biol 206:4067-79
Du, Shao Jun; Gao, Jie; Anyangwe, Victor (2003) Muscle-specific expression of myogenin in zebrafish embryos is controlled by multiple regulatory elements in the promoter. Comp Biochem Physiol B Biochem Mol Biol 134:123-34
Tan, Xungang; Du, Shao Jun (2002) Differential expression of two MyoD genes in fast and slow muscles of gilthead seabream ( Sparus aurata). Dev Genes Evol 212:207-17
Du, S J; Dienhart, M (2001) Gli2 mediation of hedgehog signals in slow muscle induction in zebrafish. Differentiation 67:84-91

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