Local juvenile hormone activity regulates gut homeostasis and tumor growth in adult Drosophila

Abstract

Hormones play essential roles during development and maintaining homeostasis in adult organisms, regulating a plethora of biological processes. Generally, hormones are secreted by glands and perform a systemic action. Here we show that Juvenile Hormones (JHs), insect sesquiterpenoids synthesized by the corpora allata, are also synthesized by the adult Drosophila gut. This local, gut specific JH activity, is synthesized by and acts on the intestinal stem cell and enteroblast populations, regulating their survival and cellular growth through the JH receptors Gce/Met and the coactivator Tai. Furthermore, we show that this local JH activity is important for damage response and is necessary for intestinal tumor growth driven by activating mutations in Wnt and EGFR/Ras pathways. Together, our results identify JHs as key hormonal regulators of gut homeostasis and open the possibility that analogous hormones may play a similar role in maintaining vertebrate adult intestinal stem cell population and sustaining tumor growth.

We are thankful to IRB Barcelona Cell separation Unit and to VDRC and Bloomington stock center for fly stocks. We thank Yolanda Rivera for technical support. We thank Jordi Casanova for comments on the manuscript. We are grateful to members of Jordi Casanova lab for constructive discussion. We thank Idun Dale Rein for FACS analysis. MMR was supported by the Marie Curie Cofund Fellowship under FP7 programme of the ERC. This work was supported by the MICINN (BFU2014-59781P) to AC and MICINN (CGL2014-55786P) and SGR-2014 from Catalan Government to XF-M and D. M. The research has also benefited from FEDER funds.