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.
| Marques, G; Musacchio, M; Shimell, M J et al. (1997) Production of a DPP activity gradient in the early Drosophila embryo through the opposing actions of the SOG and TLD proteins. Cell 91:417-26 |
