PTEN is one of the most frequently lost tumor suppressors in human cancers and regulates proliferation of stem cells and cancer cells. In a striking parallel, the C. elegans PTEN homolog,
daf-18, suppresses proliferation of primordial germ cells (PGCs). C. elegans PGCs are born during embryogenesis and normally begin to divide mid-way through the L1 stage, provided that food is present. When C. elegans hatch in the absence of food, somatic and germline development is arrested.
daf-18 is required to maintain PGC cell cycle quiescence, as
daf-18 mutant PGCs divide inappropriately when worms are starved. It was previously shown that the transcription factor DAF-16/FoxO promotes somatic cell quiescence during L1 arrest and acts downstream of DAF-18 in other contexts, but is not required for PGC quiescence. Instead, TOR has been shown to act downstream of DAF-18 in PGC quiescence regulation. We investigated the
daf-18 PGC phenotype in greater detail. We found that quiescence is maintained by either maternal or zygotic
daf-18 function, and that
daf-18 acts in the germ line to regulate PGC quiescence. We also found that
daf-18 affects PGC cell cycle in fed animals. While previous studies implicate translation in
daf-18 regulation of PGC division via TOR, our results implicate
daf-18 in germline zygotic gene activation as well. It is known that in wild-type animals, PGCs begin transcription upon feeding, as indicated by histone modifications associated with active transcription and phosphorylation of serine 2 on the RNA Pol II C-terminal tail. We found that starved
daf-18 mutant PGCs display these marks when starved WT animals do not. Consistent with these findings, inhibiting RNA Pol II with ?-amanitin partially suppresses the
daf-18 PGC division phenotype. We also observe inappropriate zygotic germline gene expression in starved
daf-18 mutants. Together, our results provide evidence for a novel DAF-18 role in germline zygotic gene activation.