Gastric Stem Cells Maintain the Adult Drosophila Stomach. Craig A. Micchelli, Marie Strand. Developmental Biology, Washington University School of Medicine, St. Louis, MO.

   The adult Drosophila copper cell region or stomach is a highly acidic compartment of the midgut with pH < 3. In this region, a specialized group of acid-secreting cells similar to mammalian gastric parietal cells has been identified by a unique ultrastructure and by copper-metallothionein fluorescence. However, the homeostatic mechanism maintaining the acid-secreting copper cells of the adult midgut has not been examined. Here, we combine cell lineage tracing and genetic analysis to investigate the mechanism by which the gastric epithelium is maintained. Our investigation shows that a molecularly identifiable population of multipotent, self-renewing gastric stem cells (GSSCs) produces the acid-secreting copper cells, interstitial cells, and enteroendocrine cells of the stomach. Our assays demonstrate that GSSCs are largely quiescent but can be induced to regenerate the gastric epithelium in response to environmental challenge. Finally, genetic analysis shows that EGFR signaling controls GSSC proliferation in the gastric epithelium. Characterization of the GSSC lineage in Drosophila, with striking similarities to mammals should advance our understanding of both homeostatic and pathogenic processes in the stomach.