384B Poster - 04. Stem cells, regeneration and tissue injury
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Faith Karanja; Rajan Bhandari; Thu Tran; Adrian Halme

Affiliation: University of Virginia

Keywords:
k. regeneration; h. intrinsic factors

Mutation of the neoplastic tumor suppressor lethal (2) giant larvae (lgl) in Drosophila melanogaster imaginal disc epithelia produces neoplastic tumors that elicit systemic responses, developmental delay, and growth inhibition, similar to those produced by regenerating imaginal discs. We observe that critical systemic and local regenerative signaling pathways are activated in lgl-mutant tumors, including expression of the relaxin-family hormone Dilp8, which is responsible for developmental delay and growth control during regeneration, and Wingless (Wg), which regulates growth and patterning in the wing during regeneration and normal development. Wg activation during regeneration is mediated by a downstream regulatory region, the damage responsive element (DRE), which we demonstrate is also responsible for Wg activation in lgl^- tumors. We observed that removal of the DRE has little effect on wingless expression during normal disc development but severely reduces the regenerative capacity of imaginal tissues and prevents neoplastic transformation as well as neoplasia-mediated developmental delay. These observations led us to hypothesize that Lgl might function to limit regenerative activity that promotes the neoplastic transformation of discs. Supporting this hypothesis, we observed that: 1) inducing damage and regeneration in imaginal discs promotes the neoplastic potential of lgl^- clones, which is blocked by removing the DRE, and 2) expression of a phosphorylation-resistant allele of Lgl strongly inhibits disc regeneration. Finally, during our analysis of lgl^- clones in the wing imaginal disc, we found unexpected heterogeneity in the neoplastic potential and the DRE dependence between clones. This heterogeneity may reflect differences in regenerative pathways and potential found in different regions of the developing tissue. These results demonstrate an unexpected role for the epithelial apical-basal polarity regulator Lgl in regulating regenerative activity in imaginal discs.