How cells acquire different determined states is the fundamental question in developmental biology. Cells are determined if they develop after transplantation according to information from their original location. Transdetermination is the phenomenon whereby determined cells alter their original fate to a new, completely different fate. The archetypal transdetermination occurs in imaginal discs, the precursors of appendages of Drosophila melanogaster, after fragmentation and prolonged periods of growth. Virtually nothing in known about the molecular basis of transdetermination. Our lab has recently made the observation that transdetermination is induced without imaginal disc fragmentation by expressing the segment polarity gene, wingless, ectopically in cell clones of pro thoracic leg imaginal discs of Drosophila (Maves and Schubiger, submitted for publication). The overall objective of this proposal is to identify other genes that cause transdetermination after ectopic expression in imaginal discs, and to group them into a functional hierarchy. For these experiments the flp-out system will be used. These experiments will lead to the creation of an inventory of transdetermination events caused by ectopic wingless expression, identification of genes in the pathway leading to transdetermination by analysis of changes in gene expression provoked by ectopic wingless expression, and determination of whether genes whose expression is altered can also induce transdetermination. Transdetermination has obvious parallels with tumorigenesis. Like transdetermination, cancer cells depart from their ancestral paths and enter new developmental pathways. In both, the new cell types result from new gene activities that are inherited in their progeny, and new patterns of growth are involved. The proposed research will lead to an understanding of how these processes occur, and will add to our understanding of the more basic question of how cells acquire different states of determination. It is hoped that ultimately this work will contribute to the understanding, prevention and treatment of tumors.
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