NEW FLY IGFS · Roles of a new family of Drosophila proteins structurally related to vertebrate insulin-like growth factors

Final Activity Report Summary - NEW FLY IGFS (Roles of a new family of Drosophila proteins structurally related to vertebrate insulin-like growth factors)

We have characterised a family of eight IGF-like genes in Drosophila. We have combined our expression and functional analyses of these genes with the expertise in structural biology in the lab of Dr Willie Taylor at NIMR to identify new members of this family in both Drosophila and other arthropods. Although these genes somewhat resemble IGFs in structure, they share a more strikingly similar cysteine arrangement to von Willebrand Factor type C repeat. Unusually for Drosophila genes, we have established that most members of this family do not seem to be expressed during embryonic or larval development and have no apparent effect on development when overexpressed from transgenes. Together with other data, this suggests that the novel family of secreted Drosophila proteins may play a role in responses to environmental stress rather than mediating IGF function. Despite the above findings, we have remained focused on the core Insulin/IGF subject of our original proposal. We have identified a novel group of insulin-producing neurons in the Drosophila nervous system. The absence of a characterised insulinergic lineage in the fruit fly had precluded investigations into the regulation of insulin production. The identification of such a lineage has allowed us to harness the powerful genetics of this model system to identify a retrograde signal and four transcription factors that regulate insulin expression. This insulinergic program shares striking similarities with that regulating insulin expression in the mammalian pancreas. Therefore, these Drosophila neurons promise to be a useful system to investigate the regulation of insulin expression and secretion.

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