The focus of this proposal is to elucidate molecular mechanisms of cartilage and bone formation. Identification of the specific molecules involved in skeletal morphogenesis may suggest treatments for degenerative diseases of the skeleton, and lead to improved methods for diagnosis and treatment of genetic disorders. Understanding mechanisms of skeletal development may serve as a paradigm for similar studies in other systems. A model will be proposed which incorporates 1) recent discoveries identifying genes critical for skeletal morphogenesis 2) characteristics of signalling pathways involving these genes 3) preliminary results describing mice which contain a null mutation in Indian hedgehog (Ihh), a gene crucial for normal skeletal development. The predictions of this model will be tested by characterizing the histology, phenotype, and patterns of expression of Parathyroid Hormone- related Protein (PTHrP), Bone Morphogenetic Protein (BMP), Patched, and Gli in the Ihh mutant. Two sets of double mutants will then be produced by simple intercross and examined to further clarify the relationship between Ihh, PTHrP, BMP, and Noggin.
| Negishi, M; van Kuik, J A; Vliegenthart, J F et al. (1992) Oligosaccharide composition of the neurotoxin-responsive sodium channel of mouse neuroblastoma and requirement of sialic acid for biological activity. Carbohydr Res 236:209-25 |
| Gilbert, F; Giovanni, M Y; Silver, I A et al. (1988) Membrane excitability expressed in human neuroblastoma cell hybrids. FEBS Lett 236:39-42 |
| Negishi, M; Glick, M C (1986) Perturbation of glycoprotein processing affects the neurotoxin-responsive Na+ channel in neuroblastoma cells. Carbohydr Res 149:185-98 |
| Emanuel, B S; Balaban, G; Boyd, J P et al. (1985) N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas. Proc Natl Acad Sci U S A 82:3736-40 |
