MOLECULAR AND CELLULAR BASIS OF LENS DEVELOPMENT

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DESCRIPTION: Embryogenesis represents a complex process whereby a single cell, the fertilized egg, gives rise to the multicellular, adult organism. In vertebrate embryos specific tissue interactions, termed inductive interactions, play a major role in determining various cell fates. The general goal of this research is to understand the molecular and cellular basis of these processes. Vertebrate lens development has served as a model system in which to examine these events, since the development of this organ is triggered by a series of specific tissue interactions. The success of this system is due to its accessibility to direct experimental manipulation, particularly in amphibian embryos. While the PI has a firm understanding of the tissue interactions involved in vertebrate lens inductions, very little is known about the molecular basis for the process of lens cell determinination, or the signaling molecules involved in lens induction. These issues are the main focus of this research proposal. Continued effort will be devoted to identifying specific changes in gene expression which are associated with the processes of lens cell determination and differentiation using the from Xenopus laevis. In Xenopus, the larval cornea can undergo transdifferentiation to form a lens. Substantial evidence indicates that this process is related to that of embryonic lens development at both the molecular and cellular levels. The phenomenon of cornea-lens transdifferentiation represents a more convenient system with which to isolate genes involved in the processes of lens cell determination and differentiation. A subtracted cDNA library, enriched in clones representing gene activity associated with the process of cornea-lens transdifferentition, will be screened. As genes are isolated, their expression will be studied during the process of embryonic lens formation, and specific tests will be conducted to determine the role they play in this process. The expression patterns of these genes, along with those the PI has already obtained, will be used as markers in tissue transplantation and tissue culture experiments to examine the role that specific tissue interactions play in triggering changes in gene expression during embryonic lens induction. Finally, experiments will be performed to determine whether specific growth factors elicit lens formation in cultures of cornea and embryonic ectodermal tissues. There is mounting evidence that growth factors play important roles in embryonic cell determination.