ArticlePloS one2010
DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Ly6d expression delineates two putative postnatal thymus epithelial progenitor cells that are differentially affected by aging.Science advances · 2026Article
- Disruption of Notch signaling by KGF induces a developmental pause in thymocytes.Frontiers in immunology · 2025Article
- Thymus Ontogeny and Development.Advances in experimental medicine and biology · 2025Review
- Recombinant FOXN1 fusion protein increases T cell generation in old mice.Frontiers in immunology · 2024Article
- Developmental dynamics of the neural crest-mesenchymal axis in creating the thymic microenvironment.Science advances · 2022Article
- Mechanical tension mobilizes Lgr6Science advances · 2022Article
- Dickkopf proteins in pathological inflammatory diseases.Journal of leukocyte biology · 2022Review
- Fine-tuning of β-catenin in mouse thymic epithelial cells is required for postnatal T-cell development.eLife · 2022Article
- WNT4 overexpression and secretion in thymic epithelial tumors drive an autocrine loop in tumor cellsFrontiers in oncology · 2022Article
- Differentiation of Pluripotent Stem Cells Into Thymic Epithelial Cells and Generation of Thymic Organoids: Applications for Therapeutic Strategies Against APECED.Frontiers in immunology · 2022Review
- Signaling Crosstalks Drive Generation and Regeneration of the Thymus.Frontiers in immunology · 2022Review
- Delayed maturation of thymic epithelium in mice with specific deletion of β-catenin gene in FoxN1 positive cells.Histochemistry and cell biology · 2021Article
- Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway.Nature communications · 2020Article
- Wnt Signaling and Its Significance Within the Tumor Microenvironment: Novel Therapeutic Insights.Frontiers in immunology · 2019Review
- MicroRNA Functions in Thymic Biology: Thymic Development and Involution.Frontiers in immunology · 2018Review
- Opposite Roles of Wnt7a and Sfrp1 in Modulating Proper Development of Neural Progenitors in the Mouse Cerebral Cortex.Frontiers in molecular neuroscience · 2018Article
- Increased epithelial-free areas in thymuses with altered EphB-mediated thymocyte-thymic epithelial cell interactions.Histochemistry and cell biology · 2017Article
- Decreased Wnt4 expression inhibits thymoma development through downregulation of FoxN1.Journal of thoracic disease · 2017Article
- FOXN1 in thymus organogenesis and development.European journal of immunology · 2016Review
- Efficient in vitro generation of functional thymic epithelial progenitors from human embryonic stem cells.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThymic epithelial cell (TEC) microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus. METHODOLOGY/PRINCIPAL
findingsHere we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+) Foxn1(+) and Aire(+) TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments. CONCLUSIONS/SIGNIFICANCE: Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic degeneration associated with cancer therapy and bone marrow transplants.
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