Tbx1 is a negative modulator of Mef2c
Bibliographic record
Abstract
The developmental role of the T-box transcription factor Tbx1 is exquisitely dosage-sensitive. In this study, we performed a microarray-based transcriptome analysis of E9.5 embryo tissues across a previously generated Tbx1 mouse allelic series. This analysis identified several genes whose expression was affected by Tbx1 dosage. Interestingly, we found that the expression of the gene encoding the cardiogenic transcription factor Mef2c was negatively correlated to Tbx1 dosage. In vivo data revealed Mef2c up-regulation in the second heart field (SHF) of Tbx1 null mutant embryos compared with wild-type littermates at E9.5. Conversely, Mef2c expression was decreased in the SHF and in somites of Tbx1 gain-of-function mutants. These results are consistent with the described role of Tbx1 in suppressing cardiac progenitor cell differentiation and indicate also a negative effect of Tbx1 on Mef2c during skeletal muscle differentiation. We show that Tbx1 occupies conserved regulatory regions of the Mef2c locus, suggesting a direct effect on Mef2c transcription. However, we also show that Tbx1 interferes with the Gata4→ Mef2c regulatory pathway. Overall, our study uncovered a target of Tbx1 with critical developmental roles, so highlighting the power of the dosage gradient approach that we used.
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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 | 0.000 | 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".