Cargando…
DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence
Quiescence, an actively-maintained reversible state of cell cycle arrest, is not well understood. PTEN is one of the most frequently lost tumor suppressors in human cancers and regulates quiescence of stem cells and cancer cells. The sole PTEN ortholog in Caenorhabditis elegans is daf-18. In a C. el...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294487/ https://www.ncbi.nlm.nih.gov/pubmed/34288923 http://dx.doi.org/10.1371/journal.pgen.1009650 |
_version_ | 1783725244382445568 |
---|---|
author | Fry, Amanda L. Webster, Amy K. Burnett, Julia Chitrakar, Rojin Baugh, L. Ryan Hubbard, E. Jane Albert |
author_facet | Fry, Amanda L. Webster, Amy K. Burnett, Julia Chitrakar, Rojin Baugh, L. Ryan Hubbard, E. Jane Albert |
author_sort | Fry, Amanda L. |
collection | PubMed |
description | Quiescence, an actively-maintained reversible state of cell cycle arrest, is not well understood. PTEN is one of the most frequently lost tumor suppressors in human cancers and regulates quiescence of stem cells and cancer cells. The sole PTEN ortholog in Caenorhabditis elegans is daf-18. In a C. elegans loss-of-function mutant for daf-18, primordial germ cells (PGCs) divide inappropriately in L1 larvae hatched into starvation conditions, in a TOR-dependent manner. Here, we further investigated the role of daf-18 in maintaining PGC quiescence in L1 starvation. We found that maternal or zygotic daf-18 is sufficient to maintain cell cycle quiescence, that daf-18 acts in the germ line and soma, and that daf-18 affects timing of PGC divisions in fed animals. Importantly, our results also implicate daf-18 in repression of germline zygotic gene activation, though not in germline fate specification. However, TOR is less important to germline zygotic gene expression, suggesting that in the absence of food, daf-18/PTEN prevents inappropriate germline zygotic gene activation and cell division by distinct mechanisms. |
format | Online Article Text |
id | pubmed-8294487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82944872021-07-31 DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence Fry, Amanda L. Webster, Amy K. Burnett, Julia Chitrakar, Rojin Baugh, L. Ryan Hubbard, E. Jane Albert PLoS Genet Research Article Quiescence, an actively-maintained reversible state of cell cycle arrest, is not well understood. PTEN is one of the most frequently lost tumor suppressors in human cancers and regulates quiescence of stem cells and cancer cells. The sole PTEN ortholog in Caenorhabditis elegans is daf-18. In a C. elegans loss-of-function mutant for daf-18, primordial germ cells (PGCs) divide inappropriately in L1 larvae hatched into starvation conditions, in a TOR-dependent manner. Here, we further investigated the role of daf-18 in maintaining PGC quiescence in L1 starvation. We found that maternal or zygotic daf-18 is sufficient to maintain cell cycle quiescence, that daf-18 acts in the germ line and soma, and that daf-18 affects timing of PGC divisions in fed animals. Importantly, our results also implicate daf-18 in repression of germline zygotic gene activation, though not in germline fate specification. However, TOR is less important to germline zygotic gene expression, suggesting that in the absence of food, daf-18/PTEN prevents inappropriate germline zygotic gene activation and cell division by distinct mechanisms. Public Library of Science 2021-07-21 /pmc/articles/PMC8294487/ /pubmed/34288923 http://dx.doi.org/10.1371/journal.pgen.1009650 Text en © 2021 Fry et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Fry, Amanda L. Webster, Amy K. Burnett, Julia Chitrakar, Rojin Baugh, L. Ryan Hubbard, E. Jane Albert DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence |
title | DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence |
title_full | DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence |
title_fullStr | DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence |
title_full_unstemmed | DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence |
title_short | DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence |
title_sort | daf-18/pten inhibits germline zygotic gene activation during primordial germ cell quiescence |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294487/ https://www.ncbi.nlm.nih.gov/pubmed/34288923 http://dx.doi.org/10.1371/journal.pgen.1009650 |
work_keys_str_mv | AT fryamandal daf18pteninhibitsgermlinezygoticgeneactivationduringprimordialgermcellquiescence AT websteramyk daf18pteninhibitsgermlinezygoticgeneactivationduringprimordialgermcellquiescence AT burnettjulia daf18pteninhibitsgermlinezygoticgeneactivationduringprimordialgermcellquiescence AT chitrakarrojin daf18pteninhibitsgermlinezygoticgeneactivationduringprimordialgermcellquiescence AT baughlryan daf18pteninhibitsgermlinezygoticgeneactivationduringprimordialgermcellquiescence AT hubbardejanealbert daf18pteninhibitsgermlinezygoticgeneactivationduringprimordialgermcellquiescence |