title: Pax8 controls thyroid follicular polarity through cadherin-16.
abstract: 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.
authors: Department of Endocrine and Nervous System Physiopathology, Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid (CSIC-UAM), Madrid 28029, Spain.
authors: Petrina
authors: P
authors: Koumarianou
authors: Bioinformatics Unit, Structural Biology Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors: Gonzalo
authors: G
authors: Goméz-López
authors: Department of Endocrine and Nervous System Physiopathology, Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid (CSIC-UAM), Madrid 28029, Spain psantisteban@iib.uam.es.
authors: Pilar
authors: 0000-0002-2758-796X
authors: P
authors: Santisteban
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D000072636:PAX8 Transcription Factor; D011509:Proteoglycans / Q000494:pharmacology; D051381:Rats; D000072637:Thyroid Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D004338:Drug Combinations; D019012:Integrin beta1; D007797:Laminin; D000072636:PAX8 Transcription Factor; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen
keywords: Cdh16; Epithelial polarity; Pax8; Thyroid follicle