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The Journal of Experimental Medicine 196 2 CD4^-CD8^- double-negative thymocytes respond to pre-TCR signaling with increased expression of Twisted gastrulation (Tsg), a gene encoding a secreted protein that binds bone morphogenetic proteins (BMPs). BMP4 is produced by thymic stroma and can interfere with the developmental progression from the CD4^-CD8^- double negative to the CD4⁺CD8⁺ double-positive stage of thymocyte development. Tsg can synergize with chordin to release thymocytes from BMP4 signals, promoting their progression to the CD4⁺CD8⁺ double positive stage. See related article by Graf et al., pp. 163-171.
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