SUMO regulates somatic cyst stem cell maintenance and directly targets the Hedgehog pathway in adult Drosophila testis

Development. 2016 May 15;143(10):1655-62. doi: 10.1242/dev.130773. Epub 2016 Mar 24.

Abstract

SUMO (Small ubiquitin-related modifier) modification (SUMOylation) is a highly dynamic post-translational modification (PTM) that plays important roles in tissue development and disease progression. However, its function in adult stem cell maintenance is largely unknown. Here, we report the function of SUMOylation in somatic cyst stem cell (CySC) self-renewal in adult Drosophila testis. The SUMO pathway cell-autonomously regulates CySC maintenance. Reduction of SUMOylation promotes premature differentiation of CySCs and impedes the proliferation of CySCs, which leads to a reduction in the number of CySCs. Consistent with this, CySC clones carrying a mutation of the SUMO-conjugating enzyme are rapidly lost. Furthermore, inhibition of the SUMO pathway phenocopies disruption of the Hedgehog (Hh) pathway, and can block the proliferation of CySCs induced by Hh activation. Importantly, the SUMO pathway directly regulates the SUMOylation of Hh pathway transcription factor Cubitus interruptus (Ci), which is required for promoting CySC proliferation. Thus, we conclude that SUMO directly targets the Hh pathway and regulates CySC maintenance in adult Drosophila testis.

Keywords: Adult stem cell; Drosophila; Hedgehog; SUMOylation; Testis.

MeSH terms

  • Aging / physiology*
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism
  • Epistasis, Genetic
  • Hedgehog Proteins / metabolism*
  • Male
  • Signal Transduction*
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Sumoylation
  • Testis / cytology*
  • Testis / metabolism

Substances

  • Drosophila Proteins
  • Hedgehog Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • hh protein, Drosophila