Drosophila MOV10 regulates the termination of midgut regeneration

Masahiko Takemura1, Nanako Bowden1, Yi-Si Lu1

  • 1Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.

Genetics
|March 11, 2021
PubMed

Insights

Stem cell regeneration requires precise control. This study identifies dMOV10 and microRNAs (miRNAs) as key regulators that halt intestinal stem cell proliferation during Drosophila midgut regeneration.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Molecular Genetics

Background:

  • Precise control of stem cell proliferation is crucial for tissue regeneration, but the underlying molecular mechanisms for terminating this process remain unclear.
  • The Drosophila midgut intestinal stem cell (ISC) model is used to investigate stem cell inactivation during regeneration.
  • Fundamental questions persist regarding how damaged tissues sense the need to stop regeneration and inactivate stem cells.

Purpose of the Study:

  • To identify novel molecular factors regulating the termination of stem cell proliferation during tissue regeneration.
  • To elucidate the role of microRNAs (miRNAs) in controlling stem cell inactivation.
  • To investigate the function of the novel gene CG6967 (dMOV10) in Drosophila midgut regeneration.

Main Methods:

  • Gene expression analysis to identify genes induced at the termination stage of regeneration.
  • RNA interference (RNAi) to assess the function of target genes and miRNAs.
  • Analysis of miRNA-mediated gene silencing pathways.
  • Identification of direct mRNA targets of dMOV10-containing miRISC.

Main Results:

  • A novel gene, dMOV10, is induced during midgut regeneration termination and inhibits ISC proliferation.
  • dMOV10 modulates the microRNA-induced silencing complex (miRISC) activity.
  • Daughter against Dpp (Dad), a BMP/TGF-β signaling inhibitor, was identified as a direct target of dMOV10-containing miRISC and is essential for ISC division.
  • Six miRNAs, including mir-1, were identified as being induced at the termination stage and are required for proper termination of ISC division.

Conclusions:

  • miRNA-mediated gene regulation plays a critical role in the precise control of Drosophila midgut regeneration.
  • dMOV10 and specific miRNAs contribute to the inactivation of stem cell proliferation, ensuring the termination of the regenerative process.
  • This study provides new insights into the molecular mechanisms governing stem cell quiescence after tissue repair.