Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in Drosophila

Abstract

Summary: Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing enteroendocrine cells or knockdown of Tachykinin leads to a similar although less severe phenotype. These results establish that enteroendocrine cells serve as an important link between diet and visceral muscle expression of an insulin-like growth factor to stimulate intestinal stem cell proliferation and tissue growth. : Amcheslavsky et al. show that enteroendocrine cells serve a niche function to regulate intestinal stem cell division. High-nutrient diet stimulates intestinal stem cell division and intestinal tissue growth in newly eclosed flies. Enteroendocrine cells act as an important link for this process by producing gut hormones such as Tachykinin to regulate the expression of an insulin-like peptide DILP3 in the visceral muscle. This Drosophila model helps to elucidate the function of enteroendocrine cells in complex whole-animal physiology.