While we have now uncovered important principles that guide how the parts of the eye are formed and integrated into a functional unit, there are serious gaps in our understanding. In general the processes governing organogenesis are very poorly understood and consequently our ability to address medically related problems are mitigated. This proposal concerns induction of the lens, an important part of the eye-forming process, and one that we have studied for many years and which has become one of the most well studied models of tissue induction. Our work has led to a five-step model for the process, beginning with a period when embryonic ectoderm is competent to respond to inductive signals, then becomes biased towards lens formation and finally specified to form a lens. Inhibitory signals restrict the region of ectoderm that will form a lens. Several hours after these events lens differentiation commences. Recent work from my laboratory has added important insights to each of these five aspects of the problem. Our recent data leads us to propose significant new directions in defining the nature of the tissue interactions associated with that particular step, and to propose strategies for definitively identifying signaling molecules involved at each point. Our research involves work with both mouse and Xenopus. The two systems are being used to determine how general the lens induction process is among vertebrates and because each system has distinct advantages. We are using a number of mouse mutant lines for defining gene products required for lens induction, and Xenopus because amphibian embryos can be so readily manipulated. This proposal also utilizes new technology we have developed for the amphibian Xenopus tropicalis which has a diploid genome and short life cycle that make it far more suitable than Xenopus laevis for genetic manipulations, for example allowing us to readily prepare transgenic lines for use in this project.
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