Diet controls normal and tumorous germline stem cells via insulin-dependent and -independent mechanisms in Drosophila.

Hsu HJ, LaFever L, Drummond-Barbosa D
Dev Biol. 2008 313 (2): 700-12

PMID: 18068153 · PMCID: PMC2254938 · DOI:10.1016/j.ydbio.2007.11.006

The external environment influences stem cells, but this process is poorly understood. Our previous work showed that germline stem cells (GSCs) respond to diet via neural insulin-like peptides (DILPs) that act directly on the germ line to upregulate stem cell division and cyst growth under a protein-rich diet in Drosophila. Here, we report that DILPs specifically control the G2 phase of the GSC cell cycle via phosphoinositide-3 kinase (PI3K) and dFOXO, and that a separate diet mediator regulates the G1 phase. Furthermore, GSC tumors, which escape the normal stem cell regulatory microenvironment, or niche, still respond to diet via both mechanisms, indicating that niche signals are not required for GSCs to sense or respond to diet. Our results document the effects of diet and insulin-like signals on the cell cycle of stem cells within an intact organism and demonstrate that the response to diet requires multiple signals. Moreover, the retained ability of GSC tumors to respond to diet parallels the long known connections between diet, insulin signaling, and cancer risk in humans.

MeSH Terms (21)

Animals Cell Cycle Cell Proliferation Cyclin E Diet Drosophila Drosophila Proteins Female Forkhead Transcription Factors G1 Phase G2 Phase Germ Cells Immunohistochemistry Insulin Models, Biological Neoplasms, Germ Cell and Embryonal Oogenesis Ovary Phosphatidylinositol 3-Kinases Signal Transduction Stem Cells

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