Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ- homolog Eip75B in Drosophila

Elife. 2020 Aug 10:9:e55795. doi: 10.7554/eLife.55795.

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: D. melanogaster; e75b/ppar; ecdysone; enteroblast; intestinal stem cell; midgut; regenerative medicine; stem cells; steroid hormone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster* / growth & development
  • Drosophila melanogaster* / metabolism
  • Ecdysone / metabolism*
  • Female
  • Gene Expression Regulation, Developmental
  • Intestines / growth & development
  • Juvenile Hormones / metabolism
  • PPAR gamma / metabolism
  • Signal Transduction
  • Stem Cells / metabolism*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Juvenile Hormones
  • PPAR gamma
  • Transcription Factors
  • Eip75B protein, Drosophila
  • Ecdysone