The long-term goal of the proposed work is to understand the role of intercellular adhesion in the development and maintenance of healthy ocular tissues of the anterior segment. While considerable progress has ben made in both the identification of cell adhesion molecules, and their structural and functional characterization in a number of developing systems, comparatively little is known regarding the nature and function of cell adhesive processes in the developing and mature lens. In order to begin to close this gap in our knowledge, experiments designed to specifically explore the expression and functional role of cadherin cell-cell adhesion molecules in lens development are proposed with the following three specific objectives.
Specific aim 1. To determine which cadherin adhesion molecules are expressed during development of the lens and to determine the timing and pattern of their expression.
Specific aim 2. To determine the functional role of cadherins during development of the lens using an in vitro model system of lens cell differentiation.
Specific aim 3. To determine the functional role of cadherins during development of the lens using in vivo immunological and molecular genetic perturbation methods. These studies will not only provide novel information regarding the regulation of expression an function of cadherin adhesion molecules during lens development, but will also shed light on the nature and role of cell- cell interactions as a regulatory mechanisms of lens cell differentiation. These studies are directly applicable to the investigations of lens pathologies which may result from aberrant lens fiber cell interactions, such as cataractogenesis.
Ferreira-Cornwell, M C; Veneziale, R W; Grunwald, G B et al. (2000) N-cadherin function is required for differentiation-dependent cytoskeletal reorganization in lens cells in vitro. Exp Cell Res 256:237-47 |