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

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 FoxNI, as a lack of functional FoxNI results in aberrant epithelial morphogenesis and an inability to attract lymphoid precursors to the thymus primordium. However, the transcriptional control of FoxnI expression has not been elucidated. Here we report that secreted Wnt glycoproteins, expressed by thymic epithelial cells and thymocytes, regulate epithelial FoxnI expression in both autocrine and paracrine fashions. Wnt molecules therefore provide regulatory signals critical for thymic function.