Abstract
Two candidate genes for controlling thymocyte differentiation,T-cellfactor-1 (Tcf-1) and lymphoid enhancer-binding factor (Lef-1), encode closely related DNA-binding HMG-box proteins1,2. Their expression pattern is complex and largely overlapping during embryogenesis, yet restricted to lymphocytes postnatally3. Here we generate two independent germline mutations in Tcf-1 and find that thymocyte development in (otherwise normal) mutant mice is blocked at the transition from the CD8+, immature single-positive to the CD4+/CD8+ double-positive stage. In contrast to wild-type mice, most of the immature single-positive cells in the mutants are not in the cell cycle and the number of immunocompetent T cells in peripheral lymphoid organs is reduced. We conclude that Tcf-1 controls an essential step in thymocyte differentiation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
van de Wetering, M., Oosterwegel, M., Dooijes, D. & Clevers, H. EMBO J. 10, 123–132 (1991).
Travis, A., Amsterdam, A., Belanger, C. & Grosschedl, R. Genes Dev. 5, 880–984 (1991).
Oosterwegel, M. et al. Development, 118, 439–448 (1993).
Godfrey, D. I. & Zlotnik, A. Immun. Today 14, 547–553 (1993).
Wilson, A., Held, W. & MacDonald, H. R. J. exp. Med. 179, 1355–1360 (1994).
van de Wetering, M. et al. J. biol. Chem. 267, 8530–8536 (1992).
Oosterwegel, M. et al. J. exp. Med. 173, 1133–1142 (1992).
MacDonald, H. R., Budd, R. C. & Howe, R. C. Eur. J. Immun. 18, 519–523 (1988).
Mombaerts, P. et al. Nature 360, 225–231 (1992).
Philpott, K. L. et al. Science 256, 1448–1452 (1992).
Molina, T. J. et al. Nature 357, 161–164 (1992).
Mombaerts, P. et al. Cell 68, 869–877 (1992).
Shinkai, Y. et al. Cell 68, 855–867 (1992).
Rahemtulla, A. et al. Nature 353, 180–184 (1991).
Fung-Leung, W-P. et al. Cell 65, 443–449 (1991).
van de Wetering, M., Oosterwegel, M., van Norren, K. & Clevers, H. EMBO J. 12, 3847–3854 (1993).
Leiden, J. A. Rev. Immun. 11, 539–570 (1993).
Clevers, H. C., Oosterwegel, M. A. & Georgopoulos, K. Immun. Today 14, 591–596 (1993).
van Genderen, C. et al. Genes Dev. 8, 2691–2703 (1994).
Giese, K., Cox, J. & Grosschedl, R. Cell 69, 185–195 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Verbeek, S., Izon, D., Hofhuis, F. et al. An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374, 70–74 (1995). https://doi.org/10.1038/374070a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/374070a0
This article is cited by
-
FAT1 expression in T-cell acute lymphoblastic leukemia (T-ALL) modulates proliferation and WNT signaling
Scientific Reports (2023)
-
Intrinsically disordered domain of transcription factor TCF-1 is required for T cell developmental fidelity
Nature Immunology (2023)
-
TCF-1 mediates chromatin intermingling during T cell development
Nature Immunology (2022)
-
TCF1 in T cell immunity: a broadened frontier
Nature Reviews Immunology (2022)
-
CD8+ T cell differentiation and dysfunction in cancer
Nature Reviews Immunology (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
