BMP-2/ALK3 and HGF signal in parallel to regulate renal collecting duct morphogenesis
Bibliographic record
Abstract
Bone morphogenetic protein (BMP)-2 and hepatocyte growth factor (HGF) exert antagonistic effects on renal collecting duct formation during embryogenesis. A current model proposes HGF inhibits BMP-2 signaling at the level of Smad1 in a common target cell. Here, we show that BMP-2 and HGF control collecting duct formation via parallel pathways. We examined the interactions between BMP-2 and HGF in the mIMCD-3 model of collecting duct morphogenesis. During tubule formation, HGF rescued the inhibitory effects of BMP-2 and of a constitutive active form of the BMP-2 receptor, ALK3, stably expressed in mIMCD-3 cells. To determine whether the effect of HGF occurs through known mediators which act downstream of the BMP-2/ALK3 complex, we examined the effect of HGF on BMP-2-induced Smad1 phosphorylation, Smad1/Smad4 complex formation, and Smad1 nuclear translocation. Neither HGF nor other receptor tyrosine kinase ligands (EGF, FGF-4) induced phosphorylation of endogenous Smad1 in mIMCD-3 cells or in Mv1Lu, MC3T3-E1 or P19 cells. Furthermore, none of these ligands blocked induction of the BMP-responsive promoter, Tlx2. Thus, HGF overcomes the inhibitory effects of BMP-2 on collecting duct morphogenesis without interrupting any of the known signaling events in the BMP-2 dependent Smad1 signaling pathway. We conclude that BMP-2/ALK3 and HGF function to control parallel pathways downstream of their respective cell surface receptors. Integration of these signals likely occurs at the level of transcriptional or post-transcriptional events.
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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 | 0.001 | 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".