Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment

Abstract Thymopoiesis strictly depends on the function of the Foxn1 transcription factor that is expressed in the thymic epithelium. During embryonic development, initial expression of the Foxn1 gene is induced in the pharyngeal endoderm by mesenchyme-derived BMP4 signals. Here, by engineering a tim...

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Autores principales:	Jeremy B. Swann, Brigitte Krauth, Christiane Happe, Thomas Boehm
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/026580411d4f43ba82d7e49d1ec1930a
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spelling	oai:doaj.org-article:026580411d4f43ba82d7e49d1ec1930a2021-12-02T11:52:33ZCooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment10.1038/s41598-017-09213-12045-2322https://doaj.org/article/026580411d4f43ba82d7e49d1ec1930a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09213-1https://doaj.org/toc/2045-2322Abstract Thymopoiesis strictly depends on the function of the Foxn1 transcription factor that is expressed in the thymic epithelium. During embryonic development, initial expression of the Foxn1 gene is induced in the pharyngeal endoderm by mesenchyme-derived BMP4 signals. Here, by engineering a time-delayed feedback system of BMP inhibition in mouse embryos, we demonstrate that thymopoiesis irreversibly fails if Foxn1 gene expression does not occur during a defining time span in mid-gestation. We also reveal an epistatic interaction between the extent of BMP signalling and the gene dosage of Foxn1. Our findings illustrate the complexities of the early steps of thymopoiesis and indicate that sporadic forms of thymic hypoplasia in humans may result from the interaction of genes affecting the magnitude of BMP signalling and Foxn1 expression.Jeremy B. SwannBrigitte KrauthChristiane HappeThomas BoehmNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeremy B. Swann Brigitte Krauth Christiane Happe Thomas Boehm Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment
description	Abstract Thymopoiesis strictly depends on the function of the Foxn1 transcription factor that is expressed in the thymic epithelium. During embryonic development, initial expression of the Foxn1 gene is induced in the pharyngeal endoderm by mesenchyme-derived BMP4 signals. Here, by engineering a time-delayed feedback system of BMP inhibition in mouse embryos, we demonstrate that thymopoiesis irreversibly fails if Foxn1 gene expression does not occur during a defining time span in mid-gestation. We also reveal an epistatic interaction between the extent of BMP signalling and the gene dosage of Foxn1. Our findings illustrate the complexities of the early steps of thymopoiesis and indicate that sporadic forms of thymic hypoplasia in humans may result from the interaction of genes affecting the magnitude of BMP signalling and Foxn1 expression.
format	article
author	Jeremy B. Swann Brigitte Krauth Christiane Happe Thomas Boehm
author_facet	Jeremy B. Swann Brigitte Krauth Christiane Happe Thomas Boehm
author_sort	Jeremy B. Swann
title	Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment
title_short	Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment
title_full	Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment
title_fullStr	Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment
title_full_unstemmed	Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment
title_sort	cooperative interaction of bmp signalling and foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/026580411d4f43ba82d7e49d1ec1930a
work_keys_str_mv	AT jeremybswann cooperativeinteractionofbmpsignallingandfoxn1genedosagedeterminesthesizeofthefunctionallyactivethymicepithelialcompartment AT brigittekrauth cooperativeinteractionofbmpsignallingandfoxn1genedosagedeterminesthesizeofthefunctionallyactivethymicepithelialcompartment AT christianehappe cooperativeinteractionofbmpsignallingandfoxn1genedosagedeterminesthesizeofthefunctionallyactivethymicepithelialcompartment AT thomasboehm cooperativeinteractionofbmpsignallingandfoxn1genedosagedeterminesthesizeofthefunctionallyactivethymicepithelialcompartment
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Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment

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