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Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans
A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types in the developi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691804/ https://www.ncbi.nlm.nih.gov/pubmed/38038410 http://dx.doi.org/10.7554/eLife.84355 |
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author | Medwig-Kinney, Taylor N Kinney, Brian A Martinez, Michael AQ Yee, Callista Sirota, Sydney S Mullarkey, Angelina A Somineni, Neha Hippler, Justin Zhang, Wan Shen, Kang Hammell, Christopher Pani, Ariel M Matus, David Q |
author_facet | Medwig-Kinney, Taylor N Kinney, Brian A Martinez, Michael AQ Yee, Callista Sirota, Sydney S Mullarkey, Angelina A Somineni, Neha Hippler, Justin Zhang, Wan Shen, Kang Hammell, Christopher Pani, Ariel M Matus, David Q |
author_sort | Medwig-Kinney, Taylor N |
collection | PubMed |
description | A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types in the developing Caenorhabditis elegans somatic gonad that derive from equipotent progenitors, but exhibit distinct cell behaviors: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We show that the fates of these cells post-specification are more plastic than previously appreciated and that levels of NHR-67 are important for discriminating between invasive and proliferative behavior. Transcription of NHR-67 is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. By screening for proteins that colocalize with NHR-67 punctae, we identified new regulators of uterine cell fate maintenance: homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1. We propose a model in which the association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo. |
format | Online Article Text |
id | pubmed-10691804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-106918042023-12-02 Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans Medwig-Kinney, Taylor N Kinney, Brian A Martinez, Michael AQ Yee, Callista Sirota, Sydney S Mullarkey, Angelina A Somineni, Neha Hippler, Justin Zhang, Wan Shen, Kang Hammell, Christopher Pani, Ariel M Matus, David Q eLife Developmental Biology A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types in the developing Caenorhabditis elegans somatic gonad that derive from equipotent progenitors, but exhibit distinct cell behaviors: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We show that the fates of these cells post-specification are more plastic than previously appreciated and that levels of NHR-67 are important for discriminating between invasive and proliferative behavior. Transcription of NHR-67 is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. By screening for proteins that colocalize with NHR-67 punctae, we identified new regulators of uterine cell fate maintenance: homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1. We propose a model in which the association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo. eLife Sciences Publications, Ltd 2023-12-01 /pmc/articles/PMC10691804/ /pubmed/38038410 http://dx.doi.org/10.7554/eLife.84355 Text en © 2023, Medwig-Kinney et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Medwig-Kinney, Taylor N Kinney, Brian A Martinez, Michael AQ Yee, Callista Sirota, Sydney S Mullarkey, Angelina A Somineni, Neha Hippler, Justin Zhang, Wan Shen, Kang Hammell, Christopher Pani, Ariel M Matus, David Q Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans |
title | Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans |
title_full | Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans |
title_fullStr | Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans |
title_full_unstemmed | Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans |
title_short | Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans |
title_sort | dynamic compartmentalization of the pro-invasive transcription factor nhr-67 reveals a role for groucho in regulating a proliferative-invasive cellular switch in c. elegans |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691804/ https://www.ncbi.nlm.nih.gov/pubmed/38038410 http://dx.doi.org/10.7554/eLife.84355 |
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