02-P006 Lgl acts antagonistically to Crumbs and aPKC to regulate the Salvador/Warts/Hippo pathway

Abstract

late onset of kidney tubule defects with abnormal cellular morphology. We have generated a Tg(phd3:GFP)/+; vhl1/+ transgenic line, which exhibit robust GFP expression in the vhl1/vhl1 background, essentially acting as an in vivo fluorescent reporter to identify the mutant cells/embryos. To induce VHL kidney tumors in fish, we have utilized this transgenic line to generate donor embryos and transplanted the mutant blastomeres to the wild type host embryos, specifically targeting these mutant cells to the renal primordium. We report that Tg(phd3:GFP) line is a live reporter for monitoring hypoxia and the induction of HIF signaling. We shall present our observations on the fate of the vhl1 mutant cells in the chimeric fish and also our analysis for the possible occurrence of neoplasia in these chimeric fish.Insufficient maternal nutrition can lead to intra-uterine growth restriction and a small-for-gestational-age fetus. Nevertheless, growth of the CNS is reduced much less dramatically than that of the rest of the body. Fetal brain sparing, which occurs at the expense of organs such as the liver, is associated in humans with adult-onset metabolic diseases, as first hypothesised by Barker in the 1980s and 1990s. Although the underlying molecular mechanisms are far from clear, brain sparing appears be a common feature of many animal species, including those that develop ex-utero.In Drosophila, we observe that dietary restriction during the late-postembryonic growth phase results in a near-normal sized CNS contained within a tiny larva. For most larval cell types, growth and division are entirely dependent upon extrinsic signals that are high under fed conditions, such as insulin and amino acids. Surprisingly, we find that neural stem-cell like progenitors (neuroblasts) are highly atypical in that they divide normally in the absence of TOR (a kinase transducing amino-acid signals) or a functional Insulin Receptor. Instead, clonal analysis indicates that neuroblast divisions are dependent upon an alternative kinase pathway that is constitutively active under both fed and starved conditions. These results identify a molecular mechanism for brain sparing and illustrate how some developing organs compete more effectively than others for limited nutritional resources. The Drosophila neoplastic tumor suppressor, Lethal-2-giantlarvae (Lgl), functions in the establishment of apico-basal cell polarity and in negatively regulating cell proliferation, however how this is achieved is little understood. Homozygous lgl À larvae show loss of apico-basal polarity in epithelial tissues. We therefore used clonal analysis (FLP/FRT) in the developing 3rd instar and pupal eye, allowing us to investigate the effects of lgl mutations in the context of surrounding wild-type tissue at various stages of development. Induction of lgl mutant clones in eye imaginal discs leads to ectopic proliferation. Further analysis shows that lgl mutants genetically interact with components of the Salvador/Warts/ Hippo (SWH) tumor suppressor pathway. Downregul...