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Notch target genes in Drosophila


The Notch (N) signaling pathway is conserved throughout the animal kingdom and is widely used during development for many cell fate and cell proliferation decisions. In particular, Notch is involved in controlling the number of neurons in both vertebrates and invertebrates, and it has also been linked to several human cancers. Despite the widespread use of this signaling pathway, very few target genes are currently known.The aim of this proposal is to identify new target genes of the N pathway. We will use the fruit fly Drosophila melanogaster as a model system, because phenotypes associated with activation or inhibition of N are very well characterized, and it allows the use of genetics to study the function and interaction of the new genes. Potential N tar get genes will be identified by DNA micro-array analysis using RNA from Drosophila cell lines or larval imaginal discs cells expressing an activated form of the N receptor. Comparing databases obtained from these different scenarios will allow us to identi fy the putative primary target genes of N signaling. These genes will be further analyzed in vivo for their relevance in the N pathway using the classical genetic tools available in the fly. Then, their function will be assessed using biochemical, molecula r and cellular studies. Our work will focus primarily on those genes for which mutants and antibodies are already available.The identification of such N target genes is of enormous interest given the recurrent use of this pathway throughout development and during normal physiology of many tissues. Furthermore, since drugs directed against core components of the N pathway are very likely to have numerous side effects, these new downstream effectors, accounting for only one part of the N response, might repre sent in this respect better drug targets.

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Trinity Lanethe Old Schools
United Kingdom