382C Poster - 04. Stem cells, regeneration and tissue injury
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Jacob Klemm; Robin Harris

Affiliation: Arizona State University

Keywords:
k. regeneration; e. necrosis

Cell death is essential for the proper regeneration of tissues following injury. Dying cells serve as crucial signaling centers that promote cell proliferation and tissue remodeling following damage. Much of our understanding of these events comes from studies in Drosophila imaginal discs. For example, apoptotic cells release Wg and Mmp1, among other factors, to adjacent cells to promote tissue repair. This phenomenon been extensively characterized with respect to apoptosis-induced regeneration, however, much less is understood about how tissues respond to unregulated forms of death, like necrosis. Necrosis is a rapid, disordered cell death in which cell membrane integrity is lost and intracellular contents are released to the external environment. To study the regenerative response to necrotic tissue death, we developed a genetic ablation system that drives necrosis in the Drosophila wing imaginal disc.
With this new model, we have found that necrosis leads to a unique regenerative response. Immunofluorescent staining reveals significant apoptosis is induced at a distance from the wound, which we have termed necrosis-induced apoptosis (NiA). Unlike other damage-associated apoptosis in the wing disc, NiA cells are not regulated by the JNK pathway. Moreover, NiA cells are required for regeneration following necrosis; inhibition of NiA cell activity leads to lower levels of proliferation at the wound edge. Consequently, NiA cell inhibition results in a reduced capacity to regenerate, as assayed by adult wing size. This research shows that upon necrotic tissue death, wing discs rely on apoptotic signaling to facilitate regeneration.
We are currently focused on identifying the signals that lead to NiA cell activity and understanding the mechanism by which these cells promote proliferation. Preliminary data highlights cytokine and calcium signaling as potential regulators of NiA cells. Additionally, lineage tracing shows NiA cell progeny may contribute to the reconstruction of the salm domain. To comprehensively identify the mechanisms that define NiA cell activity, transcriptome data will be generated for NiA cells and wound edge regenerating cells. These data will characterize the tissue response to necrosis and provide insight to designing therapeutics for humans afflicted by necrotic injuries and diseases.