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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
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.
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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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