Odd-Skipped Related 1 Regulates Bladder Development
Bibliographic record
Abstract
Background: The bladder consists of the epithelium which acts as a barrier to urine, the extracellular matrix-rich lamina propria that bears the mechanical load, and the contractile smooth muscle that expels urine. The molecular mechanisms underlying formation of these layers is largely unresolved. The transcription factor, Odd-skipped related 1 (Osr1), is an essential regulator of kidney, heart, lung and limb development, where it interacts with hedgehog (Hh), Bmp, Wnt and Fgf signaling pathways. We hypothesize that Osr1 regulates embryonic bladder development. Methods: Single-cell RNA sequencing (scRNAseq) with histological and immunofluorescent analyses were performed on wild-type and Osr1 KO mouse bladders at embryonic day (E)12 when the bladder first forms, E14 when smooth muscle arises, and E15 when the lamina propria, muscle and epithelium mature. Results: Osr1 mRNAs are expressed throughout the developing bladder. Smooth muscle and lamina propria differentiation depends on Hh, Bmp, Wnt and Fgf signaling based on scRNAseq analysis of their cognate ligands and receptors. At E12, loss of Osr1 resulted in decreased smooth muscle progenitors, while at E14, there were increased mesenchymal cell progenitors that correlated with a lack of smooth muscle cells and fibroblasts. At E15, there was less smooth muscle, a lack of suburothelial cells, no extracellular matrix, and no epithelial stratification in Osr1 KO compared to wild-type bladders (Fig.1). The morphological changes in Osr1 KO bladders arise from downregulation of Hh, Bmp, Wnt and Fgf signaling pathways at E14 (Fig.2). Conclusion: Osr1 regulates bladder patterning through interactions with Hh, Bmp, Wnt and Fgf signaling pathways. Funding: Government Support – Non-U.S.Osr1 KO bladders have increased mesenchymal cell progenitors and depletion of smooth muscle and fibroblastsHh, Bmp, Wnt and Fgf signaling pathways are downregulated in Osr1 KO bladders
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".