Abstract

This proposal is concerned with two members of the TGF-b superfamily isolated by the investigator, GDF-8 and GDF-11. GDF-8 is expressed almost exclusively in developing and adult skeletal muscle and null mutant mice show a massive and widespread increase in skeletal muscle growth. There are six aims to investigate the biological functions of GDF-8 and GDF-11.
The first aim i s to characterize the expression patterns at the RNA and protein level of GDF-8 and GDF-11. This has already been achieved for GDF-8 transcripts.
The second aim i s to characterize the phenotypes of the GDF-8 and GDF-11 null mice. The third specific aim is to purify the proteins from mammalian cells and determine the interaction between the various processed forms.
The fourth aim i s to determine the distribution of the GDF-8 and GDF-11 receptors. The fifth aim is to test the function of GDF-8 and GDF-11 protein on cultured cells to test the hypothesis that GDF-8 acts as an inhibitor of myoblast proliferation.
The final aim i s to clone the genes for the GDF-8 and GDF-11 receptors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD035887-02
Application #
2838847
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Javois, Lorette Claire
Project Start
1997-12-08
Project End
2002-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Levet, Sandrine; Ciais, Delphine; Merdzhanova, Galina et al. (2013) Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation. Blood 122:598-607
Ricard, Nicolas; Ciais, Delphine; Levet, Sandrine et al. (2012) BMP9 and BMP10 are critical for postnatal retinal vascular remodeling. Blood 119:6162-71
Lee, Young Jae; McPherron, Alexandra; Choe, Susan et al. (2010) Growth differentiation factor 11 signaling controls retinoic acid activity for axial vertebral development. Dev Biol 347:195-203
McPherron, Alexandra C; Huynh, Thanh V; Lee, Se-Jin (2009) Redundancy of myostatin and growth/differentiation factor 11 function. BMC Dev Biol 9:24
Lee, Se-Jin (2008) Genetic analysis of the role of proteolysis in the activation of latent myostatin. PLoS One 3:e1628
Lee, Se-Jin (2007) Quadrupling muscle mass in mice by targeting TGF-beta signaling pathways. PLoS One 2:e789
Lee, Se-Jin; Reed, Lori A; Davies, Monique V et al. (2005) Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci U S A 102:18117-22
Schuelke, Markus; Wagner, Kathryn R; Stolz, Leslie E et al. (2004) Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 350:2682-8
Lee, Se-Jin (2004) Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol 20:61-86
Wolfman, Neil M; McPherron, Alexandra C; Pappano, William N et al. (2003) Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases. Proc Natl Acad Sci U S A 100:15842-6

Showing the most recent 10 out of 18 publications