mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis

PLoS One. 2024 Mar 21;19(3):e0300337. doi: 10.1371/journal.pone.0300337. eCollection 2024.

Abstract

Metabolism participates in the control of stem cell function and subsequent maintenance of tissue homeostasis. How this is achieved in the context of adult stem cell niches in coordination with other local and intrinsic signaling cues is not completely understood. The Target of Rapamycin (TOR) pathway is a master regulator of metabolism and plays essential roles in stem cell maintenance and differentiation. In the Drosophila male germline, mTORC1 is active in germline stem cells (GSCs) and early germ cells. Targeted RNAi-mediated downregulation of mTor in early germ cells causes a block and/or a delay in differentiation, resulting in an accumulation of germ cells with GSC-like features. These early germ cells also contain unusually large and dysfunctional autolysosomes. In addition, downregulation of mTor in adult male GSCs and early germ cells causes non-autonomous activation of mTORC1 in neighboring cyst cells, which correlates with a disruption in the coordination of germline and somatic differentiation. Our study identifies a previously uncharacterized role of the TOR pathway in regulating male germline differentiation.

MeSH terms

  • Animals
  • Cell Differentiation
  • Drosophila / metabolism
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster* / metabolism
  • Germ Cells / metabolism
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Stem Cells
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Testis / metabolism

Substances

  • Drosophila Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases

Grants and funding

Funds to support this study were provided by the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Training Program (MC), and the NIH: AG040288, AG052732, GM135767 (DLJ): The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.