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Pax8 controls thyroid follicular polarity through cadherin-16
Organization of epithelial cells during follicular lumen formation is crucial for thyroid morphogenesis and function of the thyroid gland; however, the molecular mechanisms underlying this are poorly understood. To investigate this process, we established three-dimensional (3D) epithelial culture mo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394772/ https://www.ncbi.nlm.nih.gov/pubmed/27780871 http://dx.doi.org/10.1242/jcs.184291 |
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author | Koumarianou, Petrina Goméz-López, Gonzalo Santisteban, Pilar |
author_facet | Koumarianou, Petrina Goméz-López, Gonzalo Santisteban, Pilar |
author_sort | Koumarianou, Petrina |
collection | PubMed |
description | Organization of epithelial cells during follicular lumen formation is crucial for thyroid morphogenesis and function of the thyroid gland; however, the molecular mechanisms underlying this are poorly understood. To investigate this process, we established three-dimensional (3D) epithelial culture model systems using Fischer rat thyroid (FRT) cells or murine primary thyrocytes that developed polarized spherical structures with a central lumen, mimicking thyroid follicles. Using microarray-based differential expression analysis of FRT cells grown under 2D or 3D conditions, followed by RNA-mediated interference (RNAi) and morphogenetic analysis, we identified a key role for the thyroid transcription factor Pax8 and its target cadherin-16 (Cdh16) in the generation of polarized follicle-like structures. Silencing Pax8 expression inhibited the acquisition of apical–basal membrane polarity and impaired lumen formation. Both laminin and β1-integrin (Itgb1) expression was reduced, and cell cytoskeleton polarized distribution was altered. Silencing Cdh16 expression also led to the formation of defective structures characterized by very low laminin expression at the follicle–matrix interface, downregulation of Itgb1, and unpolarized distribution of cell cytoskeleton. Our results demonstrate that Pax8 controls apical–basal follicular polarization and follicle formation through Cdh16. |
format | Online Article Text |
id | pubmed-5394772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-53947722017-05-02 Pax8 controls thyroid follicular polarity through cadherin-16 Koumarianou, Petrina Goméz-López, Gonzalo Santisteban, Pilar J Cell Sci Research Article Organization of epithelial cells during follicular lumen formation is crucial for thyroid morphogenesis and function of the thyroid gland; however, the molecular mechanisms underlying this are poorly understood. To investigate this process, we established three-dimensional (3D) epithelial culture model systems using Fischer rat thyroid (FRT) cells or murine primary thyrocytes that developed polarized spherical structures with a central lumen, mimicking thyroid follicles. Using microarray-based differential expression analysis of FRT cells grown under 2D or 3D conditions, followed by RNA-mediated interference (RNAi) and morphogenetic analysis, we identified a key role for the thyroid transcription factor Pax8 and its target cadherin-16 (Cdh16) in the generation of polarized follicle-like structures. Silencing Pax8 expression inhibited the acquisition of apical–basal membrane polarity and impaired lumen formation. Both laminin and β1-integrin (Itgb1) expression was reduced, and cell cytoskeleton polarized distribution was altered. Silencing Cdh16 expression also led to the formation of defective structures characterized by very low laminin expression at the follicle–matrix interface, downregulation of Itgb1, and unpolarized distribution of cell cytoskeleton. Our results demonstrate that Pax8 controls apical–basal follicular polarization and follicle formation through Cdh16. The Company of Biologists Ltd 2017-01-01 /pmc/articles/PMC5394772/ /pubmed/27780871 http://dx.doi.org/10.1242/jcs.184291 Text en © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Koumarianou, Petrina Goméz-López, Gonzalo Santisteban, Pilar Pax8 controls thyroid follicular polarity through cadherin-16 |
title | Pax8 controls thyroid follicular polarity through cadherin-16 |
title_full | Pax8 controls thyroid follicular polarity through cadherin-16 |
title_fullStr | Pax8 controls thyroid follicular polarity through cadherin-16 |
title_full_unstemmed | Pax8 controls thyroid follicular polarity through cadherin-16 |
title_short | Pax8 controls thyroid follicular polarity through cadherin-16 |
title_sort | pax8 controls thyroid follicular polarity through cadherin-16 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394772/ https://www.ncbi.nlm.nih.gov/pubmed/27780871 http://dx.doi.org/10.1242/jcs.184291 |
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