Nature Immunology 3, 1102 - 1108 (2002) doi:10.1038/ni850 Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice Gina Balciunaite1, Marcel P. Keller1, Egle Balciunaite1, Luca Piali1, Saulius Zuklys1, Yves D. Mathieu1, Jason Gill2, Richard Boyd2, Daniel J. Sussman3 & Georg A. Holl?nder1 1 Pediatric Immunology, Departments of Research and Clinical-BioLogical sciences, and the Children's Hospital, University of Basel, Basel, Switzerland. 2 Department of Pathology and Immunology, Monash University, Prahran, Australia. 3 University of Maryland School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD 21201, USA. 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.