FOXC1 regulates BMP‐SMAD activity in a context dependent manner during osteogenic development events
Bibliographic record
Abstract
The forkhead box transcription factor FOXC1 is necessary for bone morphogenetic protein (BMP)‐mediated induction of early skeletogenic patterning events. We hypothesize that FOXC1 and SMAD proteins interact to regulate BMP signalling necessary for normal skeletal development. First we demonstrate that FOXC1 and SMAD5 physically interact through co‐immunoprecipitation experiments. Next we show that BMP2 enhances activation of a FOXC1‐responsive reporter gene. We tested whether FOXC1 could mediate signalling of a BMP2‐responsive reporter (2xBRE‐luc). We find that on its own, FOXC1 has no affect on activation of 2xBRE‐luc. Surprisingly, when BMP2 is added, FOXC1 inhibits activation of this reporter. Moreover, FOXC1 prevents activation of this BMP‐responsive element when SMAD4 and SMAD5 are co‐transfected along with FOXC1. To test whether FOXC1 impacted BMP2 mediated osteogenic differentation, we created C2C12 cell lines stably expressing FOXC1. We find that cells expressing FOXC1 differentiated into alkaline phosphatase‐positive osteoblasts in the absence BMP2, yet treatment of FOXC1 expressing cells with BMP2 led to no appreciable increase in alkaline phosphatase activity. Finally we show that FOXC1 prevents activation of Runx2 expression by BMP2. Together these data indicate that FOXC1 and SMAD5 proteins interact to regulate BMP‐signalling in a context dependent manner.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".