The long-range research goal of this RCDA proposal is to understand the roles of extracellular matrix (ECM) molecules in peripheral nervous system (PNS) development. ECM molecules regulate cell shape, movement and differentiation during embryogenesis, and the adhesive glycoproteins fibronectin (FN) and laminin (LAM) are located spatially and temporally to mediate aspects of neural crest differentiation and nerve fiber elongation.
Three Specific Aims define approaches to this question. First, what is the relevance of the cell binding domains of FN and LAM to cell interaction with the intact molecule? Tissue culture studies will probe 1) roles of adhesion in cell interaction with each domain, 2) behavior of living cells as they interact with specific domains, and 3) cytoskeletal correlates of these interactions. Second, how are FN and LAM used by cells in the developing PNS? Approaches will be immunocytochemistry at the light and electron microscopic levels, analysis of cell interaction with complex matrices in vitro, and perturbation of cell-ECM interactions in vivo. Third, what are the roles of defined regions of FN and LAM in migration and differentiation of neural crest cells? With RCDA funding, the P.I. will extend approaches to neural crest differentiation, but the techniques learned will be applicable to studies of neuronal behavior as well. Extended periods of time will be spent in 10 the lab of Dr. Jeremey Brockes, Kings College London, to study recombinant DNA approaches to differentiation of subpopulations of embryonic and regenerating cells, and 2) the Neuroscience Institute at the Univ. of Oregon (Eugene) where several labs are studying nervous system development in zebrafish using a wide range of techniques (eg. molecular biology, lasar ablation of cells in living animals, monoclonal antibody production). With time release from teaching and committee responsibilities, the P.I. also will be able to pursue more effectively research opportunities at the Univ. of New Mexico. In particular, the exceptional image analysis facilities at UNM will be exploited. This time will also permit the P.I. to develop a graduate course in developmental neurobiology, with the intention of attracting students to this area of research.
| Rogers, S L; Cutts, J L; Gegick, P J et al. (1994) Transforming growth factor-beta 1 differentially regulates proliferation, morphology, and extracellular matrix expression by three neural crest-derived neuroblastoma cell lines. Exp Cell Res 211:252-62 |
