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.
Highlights
Reproduction is an energetically costly process triggering multiple physiological adaptations of organs such as liver, pancreas and gastrointestinal tract upon pregnancy in various species (Hammond 1997, Roa & Tena-Sempere 2014)
Since the discovery of adult intestinal stem cells (Micchelli & Perrimon 2006, Ohlstein & Spradling 2006), local signaling pathways such as Notch (N), Jak/Stat, EGFR, Wnt/wingless, Insulin-receptor, Hippo/Warts and Dpp-signaling were shown to contribute to intestinal homeostasis under physiological and challenged conditions like bacterial infections (Miguel-Aliaga et al 2018)(and references therein)
EcR encodes for three different splice variants: EcR.A, EcR.B1 and EcR.B2 (Cherbas et al 2003, Talbot et al 1993), which we detected by PCR in intestinal tissue with highest expression for EcR.B2 (Figure 1 - figure supplement 1A)
Summary
Reproduction is an energetically costly process triggering multiple physiological adaptations of organs such as liver, pancreas and gastrointestinal tract upon pregnancy in various species (Hammond 1997, Roa & Tena-Sempere 2014). EEP, upon timely activation of scute in ISC, divide once more prior to terminal differentiation yielding a pair of EE (Chen et al 2018, Micchelli & Perrimon 2006, Ohlstein & Spradling 2006, Ohlstein & Spradling 2007). Nine out of ten ISC mitosis give rise to EB specified by N-activation in EB daughters (Micchelli & Perrimon 2006, Ohlstein & Spradling 2006, Ohlstein & Spradling 2007). Post-mitotic EB retain a certain degree of plasticity by: (1) delaying their terminal differentiation through mesenchymal-to-epithelial transition (MET) (Antonello et al 2015a), (2) changing their fate to EE upon loss of the transcription factor klu (klumpfuss) and (3) undergoing apoptosis as an additional homeostatic mechanism (Korzelius et al 2019, Reiff et al 2019)
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