Evidence map›Paper›PMID 16966428›Full record

ArticleThe Journal of experimental medicine2006

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

Ivan Maillard, LiLi Tu, Arivazhagan Sambandam, Yumi Yashiro-Ohtani, John Millholland, Karen Keeshan, Olga Shestova, Lanwei Xu, Avinash Bhandoola, Warren S Pear

Open access · greenAbstract readComparative Study
In one paragraph

Article in The Journal of experimental medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 200 citations in OpenAlex.

  1. Article
  2. Article
  3. T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025
    Review
  4. Article
  5. Review
  6. Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Early expression of mature αβ TCR in CD4Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  12. Review
  13. MonoallelicFrontiers in immunology · 2022
    Article
  14. Thymus-Derived CD4Journal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 2 countries.

Ivan MaillardDivision of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
LiLi Tu
Arivazhagan Sambandam
Yumi Yashiro-Ohtani
John Millholland
Karen Keeshan
Olga Shestova
Lanwei Xu
Avinash Bhandoola
Warren S Pear
Cancer Research Institute of the Slovak Academy of Sciences · SK

Funding

HEMATOLOGY CLINICAL RESEARCH TRAINING PROGRAMT32HL007439 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE F BRASS, PETER S KLEIN · 1985 to 2026
$17.1M
IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1M
NCI NIH HHS T32 CA009140NCI NIH HHS T32CA09140-31-35NHLBI NIH HHS T32 HL007439NHLBI NIH HHS T32HL007439-27
6 · The paper itself

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 TCRbeta expression. DNMAML attenuated the pre-TCR-associated increase in cell size and CD27 expression. TCRbeta or TCRalphabeta 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 beta-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.

Indexed as

AnimalsCell DifferentiationChromatin ImmunoprecipitationDNA PrimersFlow CytometryGene RearrangementGreen Fluorescent ProteinsMiceNuclear ProteinsReceptors, Antigen, T-CellReceptors, NotchSignal TransductionThymus GlandT-LymphocytesTranscriptional ActivationTranscription FactorsDNA PrimersGreen Fluorescent ProteinsMaml1 protein, mouseNuclear ProteinsReceptors, Antigen, T-CellReceptors, NotchTranscription Factors

Identifiers

PMID16966428
PMCPMC2118105
OpenAlexW2118233929

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.