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Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice

Nature Immunology volume 3, pages 1102–1108 (2002)Cite this article

Abstract

T cell development and selection require the fully mature and diverse epithelial microenvironment of the thymus. Acquisition of these characteristics is dependent on expression of the forkhead (also known as winged-helix) transcription factor FoxN1, as a lack of functional FoxN1 results in aberrant epithelial morphogenesis and an inability to attract lymphoid precursors to the thymus primordium. However, the transcriptional control of Foxn1 expression has not been elucidated. Here we report that secreted Wnt glycoproteins, expressed by thymic epithelial cells and thymocytes, regulate epithelial Foxn1 expression in both autocrine and paracrine fashions. Wnt molecules therefore provide regulatory signals critical for thymic function.

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Figure 1: Wnt molecules are expressed in the lymphoid and stromal compartments of the thymus.
Figure 2: Thymocytes activate the Wnt signaling pathway and target the expression of Foxn1 in TECs.
Figure 3: FoxN1 transcription is directly regulated by the Wnt signaling pathway.
Figure 4: Wnt-mediated regulation of Foxn1 transcription in TECs is controlled via the canonical pathway.
Figure 5: Wnt-mediated signaling for Foxn1 up-regulation involves PI3K and Akt.
Figure 6: Wnt and FoxN1 expression in the pharyngeal region during early thymic development.

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Acknowledgements

We thank A. Peter and I. Grass for technical assistance; G. Anderson and J. Pongracz (Birmingham, UK) for experimental help and expertise; E. Palmer, S. Arber, P. Caroni and R. Zeller for helpful discussions; and T. Mizuochi (Kyoto, Japan), H. Spits (Amsterdam, the Netherlands), G. Nolan (Stanford, USA), J. Brissette (Boston, USA), R. Kemler (Freiburg, Germany), E. R. Fearon (Ann Arbor, USA) and F. J. Staal (Rotterdam, The Netherlands) for reagents. Supported by the Swiss National Science Foundation (GAH 31-55820.98).

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Authors and Affiliations

  1. Departments of Research and Clinical-biological Sciences, Pediatric Immunology, and the Children's Hospital, University of Basel, Basel, Switzerland

    Gina Balciunaite, Marcel P. Keller, Egle Balciunaite, Luca Piali, Saulius Zuklys, Yves D. Mathieu & Georg A. Holländer

  2. Department of Pathology and Immunology, Monash University, Prahran, Australia

    Jason Gill & Richard Boyd

  3. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, 21201, MD, USA

    Daniel J. Sussman

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Balciunaite, G., Keller, M., Balciunaite, E. et al. Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat Immunol 3, 1102–1108 (2002). https://doi.org/10.1038/ni850

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