Conversion of the Thymus into a Bipotent Lymphoid Organ by Replacement of Foxn1 
with its Paralog Foxn4

Swann, Jeremy B.; Weyn, Annelies; Nagakubo, Daisuke; Bleul, Conrad C.; Toyoda, Atsushi; Happe, Christiane; Netuschil, Nikolai; Hess, Isabell; Haas-Assenbaum, Annette; Taniguchi, Yoshihito; Schorpp, Michael; Boehm, Thomas

doi:10.1016/j.celrep.2014.07.017

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Conversion of the Thymus into a Bipotent Lymphoid Organ by Replacement of Foxn1 with its Paralog Foxn4

MPS-Authors

Swann, Jeremy B.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Weyn, Annelies
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Nagakubo, Daisuke
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Bleul, Conrad C.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Happe, Christiane
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Netuschil, Nikolai
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hess, Isabell
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Haas-Assenbaum, Annette
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Schorpp, Michael
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Boehm, Thomas
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S2211124714005841?via%3Dihub
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Citation

Swann, J. B., Weyn, A., Nagakubo, D., Bleul, C. C., Toyoda, A., Happe, C., et al. (2014). Conversion of the Thymus into a Bipotent Lymphoid Organ by Replacement of Foxn1 with its Paralog Foxn4. Cell Reports, 8, 1184-1197. doi:10.1016/j.celrep.2014.07.017.

Cite as: https://hdl.handle.net/21.11116/0000-0005-C10A-6

Abstract

The thymus is a lymphoid organ unique to vertebrates, and it provides a unique microenvironment that facilitates the differentiation of immature hematopoietic precursors into mature T cells. We subjected the evolutionary trajectory of the thymic microenvironment to experimental analysis. A hypothetical primordial form of the thymus was established in mice by replacing FOXN1, the vertebrate-specific master regulator of thymic epithelial cell function, with its metazoan ancestor, FOXN4, thereby resetting the regulatory and coding changes that have occurred since the divergence of these two paralogs. FOXN4 exhibited substantial thymopoietic activity. Unexpectedly, histological changes and a functional imbalance between the lymphopoietic cytokine IL7 and the T cell specification factor DLL4 within the reconstructed thymus resulted in coincident but spatially segregated T and B cell development. Our results identify an evolutionary mechanism underlying the conversion of a general lymphopoietic organ to a site of exclusive T cell generation.