MOLECULAR AND CELLULAR BASIS OF LENS DEVELOPMENT

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Embryogeneis is a complex process whereby the fertilized egg gives rise to a multicellular adult organism. In vertebrate embryos, inductive interactions between specific tissues play a major role in determining cell fate. The vertebrate lens provides an appropriate model system to define the molecular mechanism involved in determining cell fate because development is triggered by a series of specific tissue interactions. Lens differentiation involves several stages: competence, specification and determination. Xenopus laevis represents a convenient, manipulatable system in which to study lens development because these stages have been temporally defined, as have the specific tissue interactions that are required. In Xenopus, the larval cornea can undergo transdifferentiation into lens. This process arguably reflects the natural events in lens determination and differentiation. This represents a convenient system from which to isolate genes involved in transdifferentiation and, theoretically in the various stages of embryonic lens formation. The PI has created a subtracted cDNA library enriched for genes that are specific to transdifferentiation. The library will be screened for genes potentially involved in transdifferentiation and lens induction and candidates assessed for their roles in these processes by expression studies and functional tests. The expression patterns of a number of these genes will be used to test models of lens induction in tissue transplantation experiments. Finally, experiments will be performed to identify growth factors that elicit lens formation in cultures of cornea and embryonic ectoderm tissue. Both factors suspected to play a role based on existing evidence and newly identified factors isolated from a retinal cDNA library will be tested.