|Abstract:||To regenerate, damaged tissue must heal the wound, regrow to the proper size, replace the correct cell types, and return to the normal gene-expression program. However, the mechanisms that temporally and spatially control the activation or repression of important genes during regeneration are not fully understood. In Chapter I, I review our current understanding of tissue regeneration, focusing on Drosophila imaginal disc regeneration and the known functions of chromatin regulators during tissue regeneration in diverse model organisms. In Chapter II, I describe a genetic screen for chromatin regulators that are required for epithelial tissue regeneration in response to ablation in Drosophila imaginal wing discs, which was induced through a temporally and spatially controllable genetic ablation system, to determine how chromatin regulators regulate the changes in gene expression. Many of these genes are indeed important for promoting or constraining regeneration. Specifically, the two SWI/SNF chromatin-remodeling complexes play distinct roles in regulating different aspects of regeneration, which is described in Chapter III. The PBAP complex regulates regenerative growth and developmental timing, and is required for the expression of JNK signaling targets and the growth promoter Myc. By contrast, the BAP complex is required for ensuring proper patterning and cell fate by stabilizing the expression of the posterior gene engrailed. Thus, both SWI/SNF complexes are essential for proper gene expression during tissue regeneration, but they play distinct roles in regulating growth and cell fate.
In addition to the SWI/SNF complexes, which belong to the Trithorax group (TrxG) of chromatin regulators, I investigated the roles of Polycomb, which belongs to the Polycomb Group (PcG) of chromatin regulators, during tissue regeneration, as described in Chapter IV. Reduction of Pc showed enhanced regeneration as assessed by the adult wing size after tissue regeneration, and showed an interesting rounder wing shape phenotype that is different from the phenotype of wings of BAP component mutant animals after disc regeneration. Surprisingly, the regenerative growth rate of Pc mutants was slower than controls. However, a longer delayed pupariation of the Pc mutants provided more regeneration time, which contributed to the enhanced regeneration and compensated for the slower growth rate. The upregulation of JNK signaling targets in Pc mutant regenerating discs may contribute to this prolonged regeneration time. Thus, Pc plays important roles in controlling developmental timing, maintaining proper wing shape, and regulating regenerative growth during tissue regeneration. In Chapter V, I summarize my thesis work and point out a few interesting questions for future study.