Bone Morphogenetic Proteins (BMPs) were originally identified from bone as a protein that could induce ectopic bone formation. This grant application proposes studies aimed at understanding the role of BMPs in vertebrate mesoderm patterning as well as exploration of molecular pathways of BMP signaling. Since the biochemical basis of mesoderm induction in vertebrates is perhaps best understood in the amphibian Xenopus laevis, this proposal attempts to address the involvement of BMPs by using Xenopus as the animal model. Our approach provides an opportunity to dissect the intracellular signaling cascade of BMPs, the components of which are largely unknown. Our specific plans are: (I) We will characterize the homo and heterodimeric XBMP7 in embryos. (II) Our second goal is to examine the roles of chordin, follistatin and noggin on BMP activities. We will determine whether these molecules directly antagonize BMP action using a constitutively active BMP receptor. (III) We will determine the involvement of XTALK in BMP signaling, ligand specificity, and its interaction with the type I BMP receptor using receptor/ligand cross- linking experiments. (IV) Finally, we will characterize BMP intracellular signaling processes. We will study cross-talk between the activin and BMP signaling pathways, and attempt to identify molecules involved in the BMP signaling cascade. Since BMPs are expressed in various tissues that play fundamental roles in the processes mesoderm patterning, osteogenesis, neurogenesis, and limb development, in depth knowledge of BMP signaling will likely be required for a complete understanding of embryogenesis. Insights obtained from this project will not only have broad implications for osteogenesis but are also likely to shed light into the biochemistry of TGF-beta signaling in general, an area, fundamental to processes as diverse as wound healing and tumorigenesis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02HD001158-02
Application #
2402985
Study Section
Maternal and Child Health Research Committee (HDMC)
Project Start
1996-08-01
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697