Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ-homolog Eip75B in Drosophila
Open Access
- 10 August 2020
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
Developmental studies revealed fundamental principles on how organ size and function is achieved, but less is known about organ adaptation to new physiological demands. In fruit flies, juvenile hormone (JH) induces intestinal stem cell (ISC) driven absorptive epithelial expansion balancing energy uptake with increased energy demands of pregnancy. Here, we show 20-Hydroxy-Ecdysone (20HE)-signaling controlling organ homeostasis with physiological and pathological implications. Upon mating, 20HE titer in ovaries and hemolymph are increased and act on nearby midgut progenitors inducing Ecdysone-induced-protein-75B (Eip75B). Strikingly, the PPARγ-homologue Eip75B drives ISC daughter cells towards absorptive enterocyte lineage ensuring epithelial growth. To our knowledge, this is the first time a systemic hormone is shown to direct local stem cell fate decisions. Given the protective, but mechanistically unclear role of steroid hormones in female colorectal cancer patients, our findings suggest a tumor-suppressive role for steroidal signaling by promoting postmitotic fate when local signaling is deteriorated.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (RE 34532-1)
- Wilhelm Sander-Stiftung (2018.145.1)
This publication has 101 references indexed in Scilit:
- The Ecdysone receptor constrains wingless expression to pattern cell cycle across the Drosophilawing margin in a cyclin B-dependent mannerBMC Developmental Biology, 2013
- Ecdysone receptor expression and activity in adult Drosophila melanogasterJournal of Insect Physiology, 2011
- Ecdysteroids affectDrosophilaovarian stem cell niche formation and early germline differentiationThe EMBO Journal, 2011
- Enteric Neurons and Systemic Signals Couple Nutritional and Reproductive Status with Intestinal HomeostasisCell Metabolism, 2011
- The Steroid Hormone Ecdysone Functions with Intrinsic Chromatin Remodeling Factors to Control Female Germline Stem Cells in DrosophilaCell Stem Cell, 2010
- Sex Peptide Receptor and Neuronal TOR/S6K Signaling Modulate Nutrient Balancing in DrosophilaCurrent Biology, 2010
- Colorectal Cancer Expression of Peroxisome Proliferator-Activated Receptor γ (PPARG, PPARgamma) Is Associated With Good PrognosisGastroenterology, 2009
- Allocrine Modulation of Feeding Behavior by the Sex Peptide of DrosophilaCurrent Biology, 2006
- Evidence that stem cells reside in the adult Drosophila midgut epitheliumNature, 2005
- The adult Drosophila posterior midgut is maintained by pluripotent stem cellsNature, 2005