Diet controls Drosophila Follicle Stem Cell proliferation via Hedgehog sequestration and release. Tiffiney R. Hartman, Alana O'Reilly. Fox Chase Cancer Center, Philadelphia, PA.

   A healthy diet improves adult stem cell function and delays aging-associated diseases such as cancer, heart disease, and neurodegeneration. Defining molecular mechanisms by which nutrients dictate stem cell behavior is a key step toward understanding the role of diet in tissue homeostasis. Here, we elucidate the mechanism by which dietary cholesterol controls epithelial Follicle Stem Cell (FSC) proliferation in the fly ovary. In starved flies, Hedgehog (Hh), is sequestered at the surface of Hh-producing cells within the ovary, preventing FSC proliferation. Ingestion of cholesterol initiates an S6 kinase-dependent signaling event within Hh producing cells, triggering Hh release and FSC proliferation. This mechanism enables a rapid, tissue-specific response to nutritional changes, tailoring ovarian stem cell divisions and egg production to environmental conditions sufficient for progeny survival.