The long-term objective of this proposal is to test the hypothesis that Nma is a functionally important protein involved in reciprocal epithelial-mesenchymal signaling during odontogenesis. Nma has been implicated in the pathology of melanomas that are highly metastatic and localizes to 10p11.2- 12.3. Loss of 10p12 has been reported in one of the only cytogenetic studies performed on malignant ameloblastomasas. Therefore, Nma may serve as a candidate gene that regulates oral tumor development. These studies will initially characterize Nma at the nucleic acid level, amino acid level; expression patterns, and in an in vitro knock out system utilizing antisense inhibition in whole tooth cultures. To do so, the following specific aims will be met: 1. Isolate and sequence a full-length mouse Nma cDNA clone. 2. Express recombinant Nma in E. coli, purify, characterize, and produce polyclonal antibodies directed against mouse recombinant protein. 3. Determine the temporal and spatial expression pattern of Nma and its orientation through the cell membrane. 4. Perform antisense inhibition studies on whole tooth cultures. Preliminary in situ hybridization data indicate that Nma's expression is associated with development of mineralizing tissues including dentin, enamel, alveolar bone, and hypertrophic growth plate chondrocytes. Elucidation of Nma's function during biomineralization and odontogenesis may prove useful in the grading and treatment of oral tumors such as ameloblastomas. Finally, these studies will aid in the determination of Nma's normal function during odontogenesis.
| Gonzales, C B; Simmons, D; MacDougall, M (2010) Competing roles of TGFbeta and Nma/BAMBI in odontoblasts. J Dent Res 89:597-602 |
| Knight, C; Papagerakis, P; Simmons, D et al. (2002) Genomic organization and localization of mouse Nma/BAMBI: possible implications related to ameloblastoma formation. Connect Tissue Res 43:359-64 |
