Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Koumarianou, Petrina, Goméz-López, Gonzalo, Santisteban, Pilar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2017
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
_version_ 1783229773210714112
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
work_keys_str_mv AT koumarianoupetrina pax8controlsthyroidfollicularpolaritythroughcadherin16
AT gomezlopezgonzalo pax8controlsthyroidfollicularpolaritythroughcadherin16
AT santistebanpilar pax8controlsthyroidfollicularpolaritythroughcadherin16