Direct control of somatic stem cell proliferation factors by the Drosophila testis stem cell niche

Development. 2018 Sep 3;145(17):dev156315. doi: 10.1242/dev.156315.

Abstract

Niches have traditionally been characterised as signalling microenvironments that allow stem cells to maintain their fate. This definition implicitly assumes that the various niche signals are integrated towards a binary fate decision between stemness and differentiation. However, observations in multiple systems have demonstrated that stem cell properties, such as proliferation and self-renewal, can be uncoupled at the level of niche signalling input, which is incompatible with this simplified view. We have studied the role of the transcriptional regulator Zfh1, a shared target of the Hedgehog and Jak/Stat niche signalling pathways, in the somatic stem cells of the Drosophila testis. We found that Zfh1 binds and downregulates salvador and kibra, two tumour suppressor genes of the Hippo/Wts/Yki pathway, thereby restricting Yki activation and proliferation to the Zfh1+ stem cells. These observations provide an unbroken link from niche signal input to an individual aspect of stem cell behaviour that does not, at any step, involve a fate decision. We discuss the relevance of these findings for an overall concept of stemness and niche function.

Keywords: DamID; Drosophila; Stem cell niche; Zfh1; kibra; salvador.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Proliferation / physiology*
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Male
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction / genetics
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / metabolism
  • Stem Cell Factor / metabolism
  • Stem Cell Niche / physiology*
  • Testis / cytology
  • Trans-Activators / metabolism
  • Tumor Suppressor Proteins / metabolism*
  • YAP-Signaling Proteins

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Stem Cell Factor
  • Trans-Activators
  • Tumor Suppressor Proteins
  • YAP-Signaling Proteins
  • Yki protein, Drosophila
  • kibra protein, Drosophila
  • sav protein, Drosophila
  • zfh1 protein, Drosophila
  • Site-Specific DNA-Methyltransferase (Adenine-Specific)