Elevated levels of Wnt signaling disrupt thymus morphogenesis and function

Abstract All vertebrates possess a thymus, whose epithelial microenvironment is essential for T cell development and maturation. Despite the importance of the thymus for cellular immune defense, many questions surrounding its morphogenesis remain unanswered. Here, we demonstrate that, in contrast to...

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Autores principales:	Jeremy B. Swann, Christiane Happe, Thomas Boehm
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77d9ffad1f2241eab4bd1f1a5200e4ce
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spelling	oai:doaj.org-article:77d9ffad1f2241eab4bd1f1a5200e4ce2021-12-02T15:06:09ZElevated levels of Wnt signaling disrupt thymus morphogenesis and function10.1038/s41598-017-00842-02045-2322https://doaj.org/article/77d9ffad1f2241eab4bd1f1a5200e4ce2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00842-0https://doaj.org/toc/2045-2322Abstract All vertebrates possess a thymus, whose epithelial microenvironment is essential for T cell development and maturation. Despite the importance of the thymus for cellular immune defense, many questions surrounding its morphogenesis remain unanswered. Here, we demonstrate that, in contrast to the situation in many other epithelial cell types, differentiation of thymic epithelial cells (TECs) proceeds normally in the absence of canonical Wnt signaling and the classical adhesion molecule E-cadherin. By contrast, TEC-intrinsic activation of β-catenin-dependent Wnt signaling blocks the morphogenesis of the thymus, and overexpression of a secreted Wnt ligand by TECs dominantly modifies the morphogenesis not only of the thymus, but also of the parathyroid and thyroid. These observations indicate that Wnt signaling activity in the thymus needs to be precisely controlled to support normal TEC differentiation, and suggest possible mechanisms underlying anatomical variations of the thymus, parathyroid and thyroid in humans.Jeremy B. SwannChristiane HappeThomas BoehmNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeremy B. Swann Christiane Happe Thomas Boehm Elevated levels of Wnt signaling disrupt thymus morphogenesis and function
description	Abstract All vertebrates possess a thymus, whose epithelial microenvironment is essential for T cell development and maturation. Despite the importance of the thymus for cellular immune defense, many questions surrounding its morphogenesis remain unanswered. Here, we demonstrate that, in contrast to the situation in many other epithelial cell types, differentiation of thymic epithelial cells (TECs) proceeds normally in the absence of canonical Wnt signaling and the classical adhesion molecule E-cadherin. By contrast, TEC-intrinsic activation of β-catenin-dependent Wnt signaling blocks the morphogenesis of the thymus, and overexpression of a secreted Wnt ligand by TECs dominantly modifies the morphogenesis not only of the thymus, but also of the parathyroid and thyroid. These observations indicate that Wnt signaling activity in the thymus needs to be precisely controlled to support normal TEC differentiation, and suggest possible mechanisms underlying anatomical variations of the thymus, parathyroid and thyroid in humans.
format	article
author	Jeremy B. Swann Christiane Happe Thomas Boehm
author_facet	Jeremy B. Swann Christiane Happe Thomas Boehm
author_sort	Jeremy B. Swann
title	Elevated levels of Wnt signaling disrupt thymus morphogenesis and function
title_short	Elevated levels of Wnt signaling disrupt thymus morphogenesis and function
title_full	Elevated levels of Wnt signaling disrupt thymus morphogenesis and function
title_fullStr	Elevated levels of Wnt signaling disrupt thymus morphogenesis and function
title_full_unstemmed	Elevated levels of Wnt signaling disrupt thymus morphogenesis and function
title_sort	elevated levels of wnt signaling disrupt thymus morphogenesis and function
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/77d9ffad1f2241eab4bd1f1a5200e4ce
work_keys_str_mv	AT jeremybswann elevatedlevelsofwntsignalingdisruptthymusmorphogenesisandfunction AT christianehappe elevatedlevelsofwntsignalingdisruptthymusmorphogenesisandfunction AT thomasboehm elevatedlevelsofwntsignalingdisruptthymusmorphogenesisandfunction
_version_	1718388590155661312

Elevated levels of Wnt signaling disrupt thymus morphogenesis and function

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