Interorgan regulation of Drosophila intestinal stem cell proliferation by a hybrid organ boundary zone

Development. 2017 Nov 15;144(22):4091-4102. doi: 10.1242/dev.153114. Epub 2017 Sep 25.


The molecular identities and regulation of cells at interorgan boundaries are often unclear, despite the increasingly appreciated role of organ boundaries in disease. Using Drosophila as a model, we here show that a specific population of adult midgut organ-boundary intestinal stem cells (OB-ISCs) is regulated by the neighboring hindgut, a developmentally distinct organ. This distinct OB-ISC control occurs through proximity to a specialized transition zone between the endodermal midgut and ectodermal hindgut that shares molecular signatures of both organs, which we term the hybrid zone (HZ). During homeostasis, proximity to the HZ restrains OB-ISC proliferation. However, injury to the adult HZ/hindgut drives upregulation of unpaired-3 cytokine, which signals through a Signal transducer and activator of transcription (STAT) protein to promote cell division only in OB-ISCs. If HZ disruption is severe, hyperplastic OB-ISCs expand across the interorgan boundary. Our data suggest that interorgan signaling plays an important role in controlling OB-ISCs in homeostasis and injury repair, which is likely to be crucial in prevention of disease.

Keywords: Drosophila; Hindgut; Intestinal stem cell; Midgut; Organ boundary.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning*
  • Carcinogenesis / pathology
  • Cell Cycle
  • Cell Proliferation
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / embryology*
  • Hyperplasia
  • Intestines / cytology*
  • Intestines / growth & development
  • Janus Kinases / metabolism
  • Larva / physiology
  • Models, Biological
  • Organ Specificity*
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Stem Cells / cytology*


  • Drosophila Proteins
  • STAT Transcription Factors
  • Janus Kinases