PUBLICATION
Conversion of the thymus into a bipotent lymphoid organ by replacement of FOXN1 with its paralog, FOXN4
- Authors
- Swann, J.B., Weyn, A., Nagakubo, D., Bleul, C.C., Toyoda, A., Happe, C., Netuschil, N., Hess, I., Haas-Assenbaum, A., Taniguchi, Y., Schorpp, M., Boehm, T.
- ID
- ZDB-PUB-170214-300
- Date
- 2014
- Source
- Cell Reports 8: 1184-97 (Journal)
- Registered Authors
- Boehm, Tom, Hess, Isabell, Schorpp, Michael
- Keywords
- none
- MeSH Terms
-
- Animals
- B-Lymphocytes/physiology
- Cells, Cultured
- Epithelial Cells/metabolism
- Eye Proteins/genetics*
- Eye Proteins/metabolism
- Forkhead Transcription Factors/genetics*
- Forkhead Transcription Factors/metabolism
- Gene Expression
- Genetic Engineering
- Hematopoiesis, Extramedullary
- Lymphoid Tissue
- Lymphopoiesis
- Mice
- Mice, Transgenic
- Oryzias
- Phylogeny
- T-Lymphocytes/physiology
- Thymus Gland/cytology
- Thymus Gland/metabolism*
- Zebrafish
- PubMed
- 25131198 Full text @ Cell Rep.
Citation
Swann, J.B., Weyn, A., Nagakubo, D., Bleul, C.C., Toyoda, A., Happe, C., Netuschil, N., Hess, I., Haas-Assenbaum, A., Taniguchi, Y., Schorpp, M., Boehm, T. (2014) Conversion of the thymus into a bipotent lymphoid organ by replacement of FOXN1 with its paralog, FOXN4. Cell Reports. 8:1184-97.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping