Embryonic Fibroblasts from Mice Lacking <i>Tgif</i> Were Defective in Cell Cycling
Bibliographic record
Abstract
Holoprosencephaly (HPE) is the most common structural anomaly of the human brain, resulting from incomplete cleavage of the developing forebrain during embryogenesis. Haploinsufficient mutations in the TG-interacting factor (TGIF) gene were previously identified in a subset of HPE families and sporadic patients, and this gene is located within a region of chromosome 18 that is associated with nonrandom chromosomal aberrations in HPE patients. TGIF is a three-amino-acid loop extension (TALE) homeodomain-containing transcription factor that functions both as a corepressor of the transforming growth factor beta (TGF-beta) pathway and as a competitor of the retinoic acid pathway. Here we describe mice deficient in Tgif that exhibited laterality defects and growth retardation and developed kinked tails. Cellular analysis of mutant mouse embryonic fibroblasts (MEFs) demonstrated for the first time that Tgif regulates proliferation and progression through the G1 cell cycle phase. Additionally, wild-type human TGIF was able to rescue this proliferative defect in MEFs. In contrast, a subset of human Tgif mutations detected in HPE patients was unable to rescue the proliferative defect. However, an absence of Tgif did not alter the normal inhibition of proliferation caused by treatment with TGF-beta or retinoic acid. Developmental control of proliferation by Tgif may play a role in the pathogenesis of HPE.
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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".