Early Growth Response 1 and NF-ATc1 Act in Concert to Promote Thymocyte Development beyond the β-Selection Checkpoint
Bibliographic record
Abstract
Development of immature T cell precursors beyond the beta-selection checkpoint is regulated by signals transduced by the pre-TCR complex. The pre-TCR-induced differentiation program is orchestrated by a network of transcription factors that serve to integrate this signaling information. Among these transcription factors are those of the early growth response (Egr) and NF-AT families. In this study, we demonstrate that Egr1 and NF-ATc1 act together to promote development of T cell precursors beyond the beta-selection checkpoint to the CD8 immature single-positive and CD4+ CD8+ double-positive stages. Moreover, we find that Egr1 and NF-AT cooperatively induce the expression of inhibitor of DNA binding 3 (Id3), a regulatory factor known to play an important role in positive selection of thymocytes, but not previously demonstrated to be required for beta-selection. Importantly, we show in this study that Id3 deficiency abrogates the ability of ectopically expressed Egr1 to promote traversal of the beta-selection checkpoint. Id3 is presumably essential for traversal of the beta-selection checkpoint in this context because of the inability of other inhibitor of DNA binding family members to compensate, since transgenic Egr1 does not induce expression of inhibitor of DNA binding 1 (Id1) or 2 (Id2). Taken together, these data demonstrate that Id3 is a cooperatively induced target that is important for Egr-mediated promotion of development beyond the beta-selection checkpoint. Moreover, these data indicate that the ERK and calcium signaling pathways may converge during beta-selection through the concerted action of Egr1 and NF-ATc1, respectively.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".