A genetic approach to enhancing tissue regeneration. Robin Harris, Iswar Hariharan. University of California, Berkeley, Berkeley, CA.

   In many examples of regeneration, the capacity of a tissue to regrow following damage declines with age. Understanding the mechanisms that dictate changes in regenerative capacity is vital for developing methods to stimulate or enhance regeneration. However, the underlying cellular and genetic events that lead to such changes are unknown. I am using the larval wing primordium of Drosophila - a tissue that progressively loses regenerative ability during development - to investigate the genetic mechanisms that cause a tissues regenerative response to diminish with time. I have generated a novel genetic ablation system that will be used to perform a large-scale genetic screen for genes that restore regenerative capacity in older, non-regenerating tissue. This system allows larval tissue to be ablated in a spatially and temporally controlled manner, while the extent of regeneration is assayed simply by examining adult wing tissue. Unlike previously developed ablation/regeneration systems, this system induces damage independently of the Gal4/UAS transcriptional activator, thus allowing screening to be performed using the abundant UAS-driven transgenes and purpose-made RNAi screening libraries available in Drosophila. Thus, I hope to comprehensively identify genes that comprise a regeneration program, which can be manipulated to induce regenerative growth in older, non-regenerating tissue.