Title: Molecular-genetic analysis of Drosophila melanogaster neprilysin 1-5 and Locusta migratoria ECE
Other Titles: Moleculair-genetische analyse van Drosophila melanogaster Neprilysine 1-5
Authors: Francis, Carmen
Issue Date: 13-Oct-2007
Abstract: The work presented in this thesis focuses on the identification of physiological pathways in which neprilysin-like enzymes in Drosophila melanogaster are involved. These enzymes belong to the family of M13 metalloproteases, of which neprilysin is the best characterized member in vertebrates. This class of enzymes represents important drug targets due to their contribution in the development of cardiovascular diseases, cancer and Alzheimer’s disease. Identification of these enzymes in invertebrate species offers opportunities to characterize new functions which might be conserved in vertebrates.We studied the gene expression patterns of Drosophila Nep1-Nep5 by in situ hybridization throughout development. The wide range of tissues and structures in which these enzymes are expressed suggests that they are involved in numerous physiological pathways. By performing olfactory learning tests on larvae with Nep1 overexpression in the mushroom bodies we showed that Nep1 might be involved in the process of learning and memory in flies. Localization of Nep1 antibody staining in the insulin-like peptide producing cells suggests that Nep1 may be involved in insulin signaling in Drosophila. Another interesting result we report here is the role of Nep2 in cell migration. The expression of Nep2 in ovarian border cells suggested a role of Nep2 in the migration of these cells during oogenesis. By targeting overexpression and RNAi in these migrating cells we observed delayed delamination and migration of the border cells respectively. We also show that Nep2 and maybe Nep4 are involved in the development of the embryonic tracheal system. Embryos of candidate mutant alleles for these two enzymes reveal fusion and branching defects during tracheal branching morphogenesis. Based on the differences between phenotypes produced by the alleles we suggest that Nep2 and Nep4 are implicated in different processes that contribute to the development of the tracheal system. Expression of all five neprilysins in the male reproductive organs suggests the significance of this class of enzymes in spermatogenesis and male fertility as is described for their mammalian counterparts.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Laboratory of Behavioral and Developmental Genetics
Associated Laboratories - miscellaneous (-)
Animal Physiology and Neurobiology Section - miscellaneous
Department of Human Genetics - miscellaneous

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