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Prepublished online as a Blood First Edition Paper on August 14, 2003; DOI 10.1182/blood-2003-05-1657. This Article Full Text (PDF) All Versions of this Article: 2003-05-1657v1 102/12/3947    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tsai, P. T Articles by Wu, H. Search for Related Content PubMed PubMed Citation Articles by Tsai, P. T Articles by Wu, H. Social Bookmarking                   What's this? Submitted May 23, 2003 Accepted July 24, 2003 BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis Peter T Tsai, Robert A Lee, and Hong Wu* Molecular Biology Institute, UCLA School of Medicine, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA, USA; Howard Hughes Medical Institute,, UCLA School of Medicine, Los Angeles, CA, USA * Corresponding author; email: hwu{at}mednet.ucla.edu. Thymocyte development is a non-cell-autonomous process that requires signals provided by the thymic stroma. Bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs) derived from thymic stroma have been implicated as possible regulators of T cell development. Using thymic organ culture, this study demonstrates that both BMP4 and FGF7/FGF10 arrest early T cell development at the CD4-CD8-CD44+CD25- (DN1) population and at the CD4-CD8- double negative (DN) to CD4+CD8+ double positive (DP) transition in a stromal compartment dependent manner. Furthermore, BMP4 functions upstream of FGF7/FGF10, as the effects of BMP can be suppressed by co-treatment with a FGF receptor antagonist. BMP4 also acts directly on the thymic stroma to upregulate the stroma specific transcription factor Foxn1 and stroma expressed chemokines. Taken together, this report demonstrates that BMP acts upstream of FGF in the regulation of early T cell development and that BMP4 acts primarily through the thymic stroma, thereby altering the thymic microenvironment and affecting thymopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. A. Sultana, S. Tomita, M. Hamada, Y. Iwanaga, Y. Kitahama, N. Van Khang, S. Hirai, I. Ohigashi, S. Nitta, T. Amagai, et al. Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development Blood, March 26, 2009; 113(13): 2976 - 2987. [Abstract] [Full Text] [PDF] S. W. Rossi, L. T. Jeker, T. Ueno, S. Kuse, M. P. Keller, S. Zuklys, A. V. Gudkov, Y. Takahama, W. Krenger, B. R. Blazar, et al. Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells Blood, May 1, 2007; 109(9): 3803 - 3811. [Abstract] [Full Text] [PDF] G. O. Gillard and A. G. Farr Features of Medullary Thymic Epithelium Implicate Postnatal Development in Maintaining Epithelial Heterogeneity and Tissue-Restricted Antigen Expression J. Immunol., May 15, 2006; 176(10): 5815 - 5824. [Abstract] [Full Text] [PDF] M. R. Nicolls, L. Taraseviciene-Stewart, P. R. Rai, D. B. Badesch, and N. F. Voelkel Autoimmunity and pulmonary hypertension: a perspective Eur. Respir. J., December 1, 2005; 26(6): 1110 - 1118. [Abstract] [Full Text] [PDF] C. C. Bleul and T. Boehm BMP Signaling Is Required for Normal Thymus Development J. Immunol., October 15, 2005; 175(8): 5213 - 5221. [Abstract] [Full Text] [PDF] D. B. Frank, A. Abtahi, D.J. Yamaguchi, S. Manning, Y. Shyr, A. Pozzi, H. S. Baldwin, J. E. Johnson, and M. P. de Caestecker Bone Morphogenetic Protein 4 Promotes Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension Circ. Res., September 2, 2005; 97(5): 496 - 504. [Abstract] [Full Text] [PDF]

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