EAGER: Cell Excretion, a Novel Mechanism of Cell Clearance

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Genetically programmed forms of cell death occur at a high rate throughout life in many animal tissues, necessitating rapid clearance of the resulting cell corpses to preserve tissue homeostasis. In the canonical cell clearance mechanism, remnants of apoptotic cells are engulfed by phagocytic cells and degraded in the lysosome. However, recent work has revealed that alternative forms of cell clearance are also important for meatazoan development and physiology. The objective of this proposal is to characterize one such novel process in the planarian flatworm Schmidtea mediterranea. The proposed experiments will address the hypothesis that light exposure triggers pigment cell death, but that the resulting corpses are redistributed to the gut and excreted, instead of being subjected to lysosomal degradation. Student researchers will gain valuable experience in current techniques, including RNA interference and confocal microscopy, developing skills that prepare them for scientific careers and/or graduate programs in the biological sciences. The work associated with this award will therefore augment the state of New Hampshire's efforts to expand the pipeline for future STEM professionals, a central goal of the state EPSCoR program.Preliminary data produced by the PI show that prolonged exposure to intense visible light induces complete bodily depigmentation in adult planarians and that this is associated with excretion of large amounts of heavily pigmented material from the gut. By revealing the cellular mechanisms underlying this response, the research component of this project is likely to provide new insight into how self-renewing adult tissues clear dead or damaged cells. Histologic analyses will be combined with a double-labeling approach incorporating TUNEL and fluorescent in situ hybridization (FISH) to characterize the cellular mechanisms of a light-induced depigmentation response that appears to result from selective elimination of pigment cells. The research project will significantly advance our understanding of metazoan tissue homeostasis by complementing our existing knowledge of the canonical apoptotic cell clearance pathway. Results from the study will be disseminated through scientific conference presentations and by publication in peer-reviewed journals.