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.
Highlights
Juvenile Hormones (JHs) are versatile hormones, playing major roles during larval development and in adult insects[1, 2]
JHs are acyclic sesquiterpenoids known to be synthesized by the corpus allatum (CA), a pair of endocrine glands integrated in the ring gland of insects, which in Drosophila is located above the brain hemispheres with its dorsal portion tilted anteriorly[3, 17]
We expressed each RNAi line upon the Escargot-Gal[4] driver, which is expressed in the intestinal stem cell (ISC) and EB populations of the adult midgut[6, 7], controlling the temporal expression by a temperature sensitive allele of Gal[80]
Summary
Juvenile Hormones (JHs) are versatile hormones, playing major roles during larval development and in adult insects[1, 2]. It has been recently shown that an increase in systemic JHs occurs in females after mating, which induces gut remodeling and proliferation of the intestinal stem cell (ISC) population[5]. This local, gut-specific JH production initiates an autocrine loop required for cellular growth and survival of the progenitor cell population in a Met/Gce and Tai-dependent manner. We show that Apc-Ras-induced tumors fail to grow and survive in the anterior midgut of the adult fly when the gut-specific JH activity is compromised These results open the interesting possibility that vertebrate adult intestinal stem cells may be regulated by local hormonal cues, regulating both normal tissue homeostasis and tumor growth
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