The evolutionarily conserved, secreted protein Twisted gastrulation (Tsg) modulates morphogenetic effects of decapentaplegic (dpp) and its orthologs, the bone morphogenetic proteins 2 and 4 (BMP2/4), in early Drosophila and vertebrate embryos. We have uncovered a role for Tsg at a much later stage of mammalian development, during T cell differentiation in the thymus. BMP4 is expressed by thymic stroma and inhibits the proliferation of CD4−CD8− double-negative (DN) thymocytes and their differentiation to the CD4+CD8+ double-positive (DP) stage in vitro. Tsg is expressed by thymocytes and up-regulated after T cell receptor signaling at two developmental checkpoints, the transition from the DN to the DP and from the DP to the CD4+ or CD8+ single-positive stage. Tsg can synergize with the BMP inhibitor chordin to block the BMP4-mediated inhibition of thymocyte proliferation and differentiation. These data suggest that the developmentally regulated expression of Tsg may allow thymocytes to temporarily withdraw from inhibitory BMP signals.
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15 July 2002
Article|
July 08 2002
The Developmentally Regulated Expression of Twisted Gastrulation Reveals a Role for Bone Morphogenetic Proteins in the Control of T Cell Development
Daniel Graf,
Daniel Graf
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre
3Institute of Immunology Biomedical Sciences Research Centre‘Al Fleming’, 166 72 Vari, Greece
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Suran Nethisinghe,
Suran Nethisinghe
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre
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Donald B. Palmer,
Donald B. Palmer
2Department of Immunology, Imperial College of Medicine, London W12 0NN, United Kingdom
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Amanda G. Fisher,
Amanda G. Fisher
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre
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Matthias Merkenschlager
Matthias Merkenschlager
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre
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Daniel Graf
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre
3Institute of Immunology Biomedical Sciences Research Centre‘Al Fleming’, 166 72 Vari, Greece
Suran Nethisinghe
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre
Donald B. Palmer
2Department of Immunology, Imperial College of Medicine, London W12 0NN, United Kingdom
Amanda G. Fisher
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre
Matthias Merkenschlager
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre
Address correspondence to M. Merkenschlager, Lymphocyte Development Group, Imperial College of Medicine, Hammersmith Campus, Du Cane Rd., London W12 0NN, UK. Phone: 44-208-383-8236; Fax: 44-208-383-8338; E-mail: [email protected]
*
Abbreviations used in this paper: BMP, bone morphogenetic protein; DN, double negative; DP, double positive; dpp, decapentaplegic; pSmad, phospho-Smad; Rag, recombination activating gene; RT, reverse transcription; sog, short gastrulation; SP, single positive; Tsg, twisted gastrulation.
Received:
February 20 2002
Revision Received:
April 29 2002
Accepted:
May 30 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 196 (2): 163–171.
Article history
Received:
February 20 2002
Revision Received:
April 29 2002
Accepted:
May 30 2002
Citation
Daniel Graf, Suran Nethisinghe, Donald B. Palmer, Amanda G. Fisher, Matthias Merkenschlager; The Developmentally Regulated Expression of Twisted Gastrulation Reveals a Role for Bone Morphogenetic Proteins in the Control of T Cell Development . J Exp Med 15 July 2002; 196 (2): 163–171. doi: https://doi.org/10.1084/jem.20020276
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