PgmNr D1063: Drosophila Wnt and STAT Define Apoptosis-Resistant Epithelial Cells for Tissue Regeneration after Irradiation.

Authors:
S. Verghese; T. T. Su


Institutes
University of Colorado, Boulder, CO.


Keyword: apoptosis

Abstract:

Drosophila larvae irradiated with doses of ionizing radiation (IR) that kill about half of the cells in larval imaginal discs still develop into viable adults. How surviving cells compensate for IR-induced cell death to produce organs of normal size and appearance remains an active area of investigation. We have identified a subpopulation of cells within the continuous epithelium of Drosophila larval wing discs that shows intrinsic resistance to ionizing radiation (IR)- and drug-induced apoptosis. These cells reside in domains of high Wingless (Wg, Drosophila Wnt-1) and STAT92E (sole Drosophila STAT homolog) activity, and would normally form the hinge in the adult fly. Resistance to IR-induced apoptosis requires STAT and Wg, and is mediated by transcriptional repression of pro-apoptotic gene reaper. Lineage tracing experiments show that, following irradiation, apoptosis-resistant cells lose their identity and translocate to areas of the wing disc that suffered abundant cell death where they assume appropriate new identities. Our findings provide a new paradigm for regeneration in which it is unnecessary to invoke special damage-resistant cell types such as stem cells. Instead, differences in gene expression within a population of genetically identical epithelial cells can create a subpopulation with greater resistance, which, following damage, survive, alter their fate, and help regenerate the tissue.



Flybase Genetic Index:
1. FlyBase gene symbol: STAT92E; FBgn: FBgn0016917
2. FlyBase gene symbol: Wg; FBgn: FBgn0004009
3. FlyBase gene symbol: reaper; FBgn: FBgn0011706