Classic experimental approaches to regeneration have provided insight into three conserved aspects of the process: wound healing, formation of a """"""""blastema"""""""" consisting of pluripotent, highly proliferative cells, and pattern regulation. This study proposes to study these processes at the molecular level by mapping the expression patterns, and also manipulating the functions, of genes involved in patterning and cell cycle control in the leg primordia of Drosophila, called imaginal discs. The preliminary data provided shows that a central player in normal and regenerative limb development is the secreted signal wingless. Homologs of wingless have analogous function in vertebrate limb patterning and regeneration, such as wound healing, transplantation and chemotherapy. Studies in Drosophila are advantageous because the system has advanced tools for genetic manipulation.
The first aim of this proposal is to provide a molecular description of the sequence of patterning gene expression and function during imaginal leg disc regeneration, and in so doing to define the roles wingless and other secreted signals such as dpp play in the process.
The second aim i s to identify which of the known cell cycle genes control cell proliferation in regeneration blastemas, and to link regulation of these genes to the patternin cues that promote blastema growth.
The third aim i s to identify new genes that interact with wingless during regeneration, using a novel genetic screen. The findings will allow specific working hypotheses to be developed pertaining to cell cycle control, wound healing and growth during regeneration.
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