ArticlePLoS genetics2011
Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 159 citations in OpenAlex.
- Inducible kidney-selective knockdown of Cyp27b1 does not compromise calcium and bone homeostasis.Journal of endocrinological investigation · 2026Article
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Combinatory differentiation of human induced pluripotent stem cells generates functional thymic epithelium driving dendritic cell and CD4/CD8 T cell development.Nature communications · 2026Article
- Premature thymic involution in young Foxn1lacz mutant mice causes peripheral T cell phenotypes similar to aging-induced immunosenescence.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Insulin-like growth factor 2 as a driving force for exponential expansion and differentiation of the neonatal thymus.Development (Cambridge, England) · 2025Article
- Thymic inborn errors of immunity.The Journal of allergy and clinical immunology · 2025Review
- Thymus Ontogeny and Development.Advances in experimental medicine and biology · 2025Review
- Generation and repair of thymic epithelial cells.The Journal of experimental medicine · 2024Review
- Age-related epithelial defects limit thymic function and regeneration.Nature immunology · 2024Article
- Mechanisms underlying the direct programming of mouse embryonic fibroblasts to thymic epithelial cells by FOXN1.Development (Cambridge, England) · 2024Article
- Primary and secondary defects of the thymus.Immunological reviews · 2024Review
- MicroRNAs as the Critical Regulators of Forkhead Box Protein Family in Pancreatic, Thyroid, and Liver Cancers.Biochemical genetics · 2023Review
- Administration of recombinant FOXN1 protein attenuates Alzheimer's pathology in mice.Brain, behavior, and immunity · 2023Article
- Foxn1 overexpression promotes thymic epithelial progenitor cell proliferation and mTEC maintenance, but does not prevent thymic involution.Development (Cambridge, England) · 2023Article
- Human thymus in health and disease: Recent advances in diagnosis and biology.Seminars in immunology · 2023Review
- Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis.Frontiers in immunology · 2023Article
- Article
- Delta-like 4-Derived Notch Signals Differentially Regulate Thymic Generation of Skin-Homing CCR10Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Inborn errors of immunity associated with defects of thymic development.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022Review
- Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The forkhead transcription factor Foxn1 is indispensable for thymus development, but the mechanisms by which it mediates thymic epithelial cell (TEC) development are poorly understood. To examine the cellular and molecular basis of Foxn1 function, we generated a novel and revertible hypomorphic allele of Foxn1. By varying levels of its expression, we identified a number of features of the Foxn1 system. Here we show that Foxn1 is a powerful regulator of TEC differentiation that is required at multiple intermediate stages of TE lineage development in the fetal and adult thymus. We find no evidence for a role for Foxn1 in TEC fate-choice. Rather, we show it is required for stable entry into both the cortical and medullary TEC differentiation programmes and subsequently is needed at increasing dosage for progression through successive differentiation states in both cortical and medullary TEC. We further demonstrate regulation by Foxn1 of a suite of genes with diverse roles in thymus development and/or function, suggesting it acts as a master regulator of the core thymic epithelial programme rather than regulating a particular aspect of TEC biology. Overall, our data establish a genetics-based model of cellular hierarchies in the TE lineage and provide mechanistic insight relating titration of a single transcription factor to control of lineage progression. Our novel revertible hypomorph system may be similarly applied to analyzing other regulators of development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.