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Conversion of the thymus into a bipotent lymphoid organ by replacement of FOXN1 with its paralog, FOXN4.
- Source :
-
Cell reports [Cell Rep] 2014 Aug 21; Vol. 8 (4), pp. 1184-97. Date of Electronic Publication: 2014 Aug 14. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
B-Lymphocytes physiology
Cells, Cultured
Epithelial Cells metabolism
Eye Proteins metabolism
Forkhead Transcription Factors metabolism
Gene Expression
Genetic Engineering
Hematopoiesis, Extramedullary
Lymphoid Tissue
Lymphopoiesis
Mice
Mice, Transgenic
Oryzias
Phylogeny
T-Lymphocytes physiology
Thymus Gland cytology
Zebrafish
Eye Proteins genetics
Forkhead Transcription Factors genetics
Thymus Gland metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 25131198
- Full Text :
- https://doi.org/10.1016/j.celrep.2014.07.017