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The Journal of Immunology, 2008, 181, 5272 -5277
Copyright © 2008 by The American Association of Immunologists, Inc.
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Maintenance of Thymic Epithelial Phenotype Requires Extrinsic Signals in Mouse and Zebrafish1

Cristian Soza-Ried2, Conrad C. Bleul2, Michael Schorpp and Thomas Boehm3

Department of Developmental Immunology, Max-Planck Institute of Immunobiology, Stuebeweg, Freiburg, Germany

Thymopoiesis strictly depends on proper differentiation of the thymic epithelial anlage. Differentiation of thymic epithelial cells (TECs) is controlled by the Foxn1 transcription factor. The in vivo signals initiating and maintaining Foxn1 expression in the future thymus anlage are unknown. In the mouse, bone morphogenetic protein (BMP) signaling is required for the maintenance of Foxn1 expression in TECs, as shown here by lineage tracing using a Foxn1-driven Cre transgene. Loss of Foxn1 expression after BMP inhibition reverts TECs to a basal state of pharyngeal epithelium unable to support T cell development; it does not divert them into a parathyroid fate. In zebrafish larvae, BMP inhibition likewise causes loss of foxn1 expression in the thymic anlage and subsequent impairment of thymopoiesis. These results indicate an evolutionarily conserved role of BMP signaling in the maintenance of Foxn1 expression.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by the Max-Planck Society and the Deutsche Forschungsgemeinschaft.

2 C.S.-R. and C.C.B. contributed equally to this work and should be considered joint first authors.

3 Address correspondence and reprint requests to Dr. Thomas Boehm. Max Planck Institute of Immunobiology, Freiburg, Germany. E-mail address: boehm{at}immunbio.mpg.de

4 Abbreviations used in this paper: BMP, bone morphogenetic protein; TEC, thymic epithelial cell; hpf, hours post fertilization.


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