The Developmentally Regulated Expression of <i>Twisted Gastrulation</i> Reveals a Role for Bone Morphogenetic Proteins in the Control of T Cell Development

Journal article

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

Authors: Graf, D; Nethisinghe, S; Palmer, DB; Fisher, AG; Merkenschlager, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Rockefeller University Press
• Journal: Journal of Experimental Medicine
• Volume: 196
• Issue: 2
• Pages: 163-171
• Publication date: 2002-07-08
• DOI: 10.1084/jem.20020276
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Gene; Immune system; Decapentaplegic; Cell biology; In vitro; Embryo; Biology; Bone morphogenetic protein; Embryogenesis; Gastrulation; Genetics; Imaginal disc; Immunology; CD8; Bone morphogenetic protein 2; Thymocyte; Drosophila melanogaster; Bone morphogenetic protein 4; Chordin