Bibliographic record
Abstract
Developmental anomalies of the bladder pose a great challenge to pediatric urologists. Yet the mechanisms regulating the developmental biology of the bladder remain poorly understood. Bladder development involves epithelial-mesenchymal interaction. p63 is expressed in all stratified epithelia including the bladder urothelium. We have established that the N-terminal truncated isoform of p63, ΔNp63, is preferentially expressed in the ventral bladder urothelium during early organogenesis. p63-/- embryos embryos developed ventral midline defects affecting the ventral bladder and abdominal walls, reminiscent of bladder exstrophy, a congenital anomaly exhibited in human neonates. The p63 deficient ventral urothelium was neither stratified nor differentiated. It had significantly increased apoptotic activity and reduced cell proliferation. This is accompanied by failure to induce mesenchyme. Over-expression of ΔNp63 in p63-/- bladder primary cell cultures rescued the apoptosis. We conclude that ΔNp63 plays a crucial anti-apoptotic role during bladder development. The absence of ΔNp63 leads to ventral urothelial apoptosis, failure of mesenchymal development and bladder exstrophy. Shh is a candidate epithelial signal in the bladder epithelial mesenchymal interaction. The mechanism by which Shh regulates bladder development remains unclear. In the wild-type developing bladders, Shh was expressed in the epithelium whereas its transcriptional factor Gli2 and its target gene Bmp4 were expressed in the inner mesenchymal zone, which also contained more proliferating cells. In the outer mesenchymal zone, where Gli2 and Bmp4 expressions were not detectable, smooth muscle α-actin expression was detected. In Gli2 -/- embryo bladders, normal Bmp4 expression in the inner zone was lost. The normal radial pattern of inner zone of cell proliferation and outer zone of smooth muscle differentiation was replaced by disorganized cell proliferation and ectopic smooth muscle in the inner zone. Using primary murine bladder mesenchymal cell cultures, we demonstrated that transfection with ΔNGli2 adenoviruses up-regulated Bmp4 expression and addition of Bmp4 protein (10mg/ml) repressed smooth muscle differentiation. We conclude that Shh transcriptional factor Gli2 regulates the bladder mesenchymal patterning.
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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) | 0.002 | 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".