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Bioinformatic and experimental analysis of hox and epidermal wound response enhancers in Drosophila

Abstract

Unlike the well-known correspondence between the mRNA sequence blueprint and the protein encoded from it, fairly little is understood about how cis-regulatory elements, the DNA sequences that control when and where mRNAs are expressed, are structured to exert their influence. Even genes with well-conserved expression patterns in distantly related organisms, such as Dll in developing limbs of protostomes and deuterostomes, are controlled by largely unknown mechanisms. The number of techniques available for understanding cis-regulation is expanding rapidly, but each one has severe limitations. In an attempt to improve the rate of cis-regulatory discovery, I have combined molecular biological and in silico techniques to study two cis-regulatory paradigms in Drosophila. To dissect the cis -regulatory mechanisms controlling Dll limb expression in insects, I used germline transformation and bioinformatics to identify several novel motifs required for embryonic limb expression of Dll. Based on the techniques developed studying Dll, I have extended previous research dissecting a cis-regulatory element controlling Ddc wound-induced expression. I have identified a battery of wound-response genes, including the particular cis-regulatory elements controlling wound-responsive expression. These elements reveal complex regulatory interactions that result in the induction of a diverse set of genes required for various aspects of Drosophila wound healing

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