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Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity
Planar cell polarity (PCP) is essential for tissue morphogenesis and homeostasis; however, the mechanisms that orchestrate the cell shape and packing dynamics required to establish PCP are poorly understood. Here, we identified a major role for the globular (G)-actin-binding protein thymosin-β4 (TMS...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758630/ https://www.ncbi.nlm.nih.gov/pubmed/33310787 http://dx.doi.org/10.1242/dev.193425 |
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author | Padmanabhan, Krishnanand Grobe, Hanna Cohen, Jonathan Soffer, Arad Mahly, Adnan Adir, Orit Zaidel-Bar, Ronen Luxenburg, Chen |
author_facet | Padmanabhan, Krishnanand Grobe, Hanna Cohen, Jonathan Soffer, Arad Mahly, Adnan Adir, Orit Zaidel-Bar, Ronen Luxenburg, Chen |
author_sort | Padmanabhan, Krishnanand |
collection | PubMed |
description | Planar cell polarity (PCP) is essential for tissue morphogenesis and homeostasis; however, the mechanisms that orchestrate the cell shape and packing dynamics required to establish PCP are poorly understood. Here, we identified a major role for the globular (G)-actin-binding protein thymosin-β4 (TMSB4X) in PCP establishment and cell adhesion in the developing epidermis. Depletion of Tmsb4x in mouse embryos hindered eyelid closure and hair-follicle angling owing to PCP defects. Tmsb4x depletion did not preclude epidermal cell adhesion in vivo or in vitro; however, it resulted in abnormal structural organization and stability of adherens junction (AJ) due to defects in filamentous (F)-actin and G-actin distribution. In cultured keratinocytes, TMSB4X depletion increased the perijunctional G/F-actin ratio and decreased G-actin incorporation into junctional actin networks, but it did not change the overall actin expression level or cellular F-actin content. A pharmacological treatment that increased the G/F-actin ratio and decreased actin polymerization mimicked the effects of Tmsb4x depletion on both AJs and PCP. Our results provide insights into the regulation of the actin pool and its involvement in AJ function and PCP establishment. |
format | Online Article Text |
id | pubmed-7758630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77586302020-12-30 Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity Padmanabhan, Krishnanand Grobe, Hanna Cohen, Jonathan Soffer, Arad Mahly, Adnan Adir, Orit Zaidel-Bar, Ronen Luxenburg, Chen Development Research Article Planar cell polarity (PCP) is essential for tissue morphogenesis and homeostasis; however, the mechanisms that orchestrate the cell shape and packing dynamics required to establish PCP are poorly understood. Here, we identified a major role for the globular (G)-actin-binding protein thymosin-β4 (TMSB4X) in PCP establishment and cell adhesion in the developing epidermis. Depletion of Tmsb4x in mouse embryos hindered eyelid closure and hair-follicle angling owing to PCP defects. Tmsb4x depletion did not preclude epidermal cell adhesion in vivo or in vitro; however, it resulted in abnormal structural organization and stability of adherens junction (AJ) due to defects in filamentous (F)-actin and G-actin distribution. In cultured keratinocytes, TMSB4X depletion increased the perijunctional G/F-actin ratio and decreased G-actin incorporation into junctional actin networks, but it did not change the overall actin expression level or cellular F-actin content. A pharmacological treatment that increased the G/F-actin ratio and decreased actin polymerization mimicked the effects of Tmsb4x depletion on both AJs and PCP. Our results provide insights into the regulation of the actin pool and its involvement in AJ function and PCP establishment. The Company of Biologists Ltd 2020-12-13 /pmc/articles/PMC7758630/ /pubmed/33310787 http://dx.doi.org/10.1242/dev.193425 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This 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 that the original work is properly attributed. |
spellingShingle | Research Article Padmanabhan, Krishnanand Grobe, Hanna Cohen, Jonathan Soffer, Arad Mahly, Adnan Adir, Orit Zaidel-Bar, Ronen Luxenburg, Chen Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity |
title | Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity |
title_full | Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity |
title_fullStr | Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity |
title_full_unstemmed | Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity |
title_short | Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity |
title_sort | thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758630/ https://www.ncbi.nlm.nih.gov/pubmed/33310787 http://dx.doi.org/10.1242/dev.193425 |
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