DOI: 10.1084/jem.20061020. The requirement for Notch signaling at the β-selection checkpoint in vivo is absolute and independent of the pre

The requirement for Notch signaling at the β-selection checkpoint in vivo is absolute and independent of the pre–T cell receptor

10.1084/jem.20061020

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Genetic inactivation of Notch signaling in CD4−CD8− double-negative (DN) thymocytes was previously shown to impair T cell receptor (TCR) gene rearrangement and to cause a partial block in CD4+CD8+ double-positive (DP) thymocyte development in mice. In contrast, in vitro cultures suggested that Notch was absolutely required for the generation of DP thymocytes independent of pre-TCR expression and activity. To resolve the respective role of Notch and the pre-TCR, we inhibited Notch-mediated transcriptional activation in vivo with a green fluorescent protein–tagged dominant-negative Mastermind-like 1 (DNMAML) that allowed us to track single cells incapable of Notch signaling. DNMAML expression in DN cells led to decreased production of DP thymocytes but only to a modest decrease in intracellular TCRβ expression. DNMAML attenuated the pre-TCR–associated increase in cell size and CD27 expression. TCRβ or TCRαβ transgenes failed to rescue DNMAML-related defects. Intrathymic injections of DNMAML− or DNMAML+ DN thymocytes revealed a complete DN/DP transition block, with production of DNMAML+ DP thymocytes only from cells undergoing late Notch inactivation. These findings indicate that the Notch requirement during the β-selection checkpoint in vivo is absolute and independent of the pre-TCR, and it depends on transcriptional activation by Notch via the CSL/RBP-J–MAML complex.

Bibliography

Maillard, I., Tu, L., Sambandam, A., Yashiro-Ohtani, Y., Millholland, J., Keeshan, K., Shestova, O., Xu, L., Bhandoola, A., & Pear, W. S. (2006). The requirement for Notch signaling at the Î²-selection checkpoint in vivo is absolute and independent of the preâT cell receptor. The Journal of Experimental Medicine, 203(10), 2239â2245.

Authors 10

Ivan Maillard (first)
LiLi Tu (additional)
Arivazhagan Sambandam (additional)
Yumi Yashiro-Ohtani (additional)
John Millholland (additional)
Karen Keeshan (additional)
Olga Shestova (additional)
Lanwei Xu (additional)
Avinash Bhandoola (additional)
Warren S. Pear (additional)

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Dates

Type	When
Created	18 years, 11 months ago (Sept. 11, 2006, 8:31 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 9:39 a.m.)
Indexed	3 months ago (June 3, 2025, 12:26 a.m.)
Issued	18 years, 11 months ago (Sept. 11, 2006)
Published	18 years, 11 months ago (Sept. 11, 2006)
Published Online	18 years, 11 months ago (Sept. 11, 2006)
Published Print	18 years, 11 months ago (Oct. 2, 2006)

Funders 0

None

BibTeX

@article{Maillard_2006, title={The requirement for Notch signaling at the β-selection checkpoint in vivo is absolute and independent of the pre–T cell receptor}, volume={203}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20061020}, DOI={10.1084/jem.20061020}, number={10}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Maillard, Ivan and Tu, LiLi and Sambandam, Arivazhagan and Yashiro-Ohtani, Yumi and Millholland, John and Keeshan, Karen and Shestova, Olga and Xu, Lanwei and Bhandoola, Avinash and Pear, Warren S.}, year={2006}, month=sep, pages={2239–2245} }

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