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DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence

Amanda L Fry1, Amy K Webster2, Julia Burnett1

  • 1Skirball Institute of Biomolecular Medicine, Department of Cell Biology, NYU Grossman School of Medicine, New York, New York, United States of America.

Plos Genetics
|July 21, 2021
PubMed

Insights

The tumor suppressor PTEN (phosphatase and tensin homolog) maintains cell cycle arrest in C. elegans. Loss of daf-18/PTEN causes premature germ cell division during starvation, highlighting its role in quiescence.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Quiescence is a crucial, yet poorly understood, reversible cell cycle arrest state.
  • PTEN (phosphatase and tensin homolog) is a key tumor suppressor regulating stem and cancer cell quiescence.
  • The C. elegans daf-18 gene is the sole ortholog of PTEN.

Purpose of the Study:

  • To investigate the role of daf-18 in maintaining primordial germ cell (PGC) quiescence in C. elegans L1 larvae under starvation conditions.
  • To elucidate the mechanisms by which daf-18/PTEN regulates PGC cell cycle arrest and germline gene expression.

Main Methods:

  • Utilized loss-of-function mutants of daf-18 in C. elegans.
  • Observed PGC behavior and cell cycle progression under starvation and fed conditions.
  • Assessed the impact of daf-18 on germline zygotic gene activation and TOR signaling pathways.

Main Results:

  • Maternal or zygotic daf-18 is sufficient for maintaining PGC quiescence during L1 starvation.
  • daf-18 functions in both germline and somatic cells to regulate PGC divisions.
  • daf-18 represses germline zygotic gene activation, independent of TOR signaling, suggesting distinct regulatory mechanisms.

Conclusions:

  • daf-18/PTEN is essential for preventing inappropriate PGC division and germline gene activation during starvation in C. elegans.
  • daf-18/PTEN employs distinct mechanisms to control cell cycle arrest and gene expression, highlighting its multifaceted role in quiescence maintenance.

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