Role of Core Planar Cell Polarity Vangl2 Gene in the Renal Tubule Development in Mice
Bibliographic record
Abstract
Background: Polycystic kidney disease (PKD) is a common kidney disease that affects the development and maintenance of renal tubules, leads to cyst formation, and often progresses to end-stage kidney disease. It has been postulated that defective planar cell polarity (PCP) signaling contributes to initiation of cyst formation in PKD via controlling both convergent extension (CE, a process of directional cell movements) and oriented cell division (OCD, a process of directional cell divisions during tubular elongation post-natally). Indeed, mutations of the key PCP gene, Van Gogh-like 2 (Vangl2), lead to abnormal renal tubules in murine embryonic kidneys, correlating with the original postulate. Methods: In order to further understand the influence of the Vangl2 gene on renal morphogenesis and cystogenesis, control and Vangl2 mutant embryos—as well as post-natal Vangl2 mice with conditional excision of the Vangl2 gene in renal collecting tubules—were generated, then analyzed using immunostaining and fluorescence microscopy. Results: Our results show that Vangl2 plays a role in CE and apical constriction (AC) during embryonic stage of tubulogenesis. Compared to control animals, mutant Vangl2Δ/Δ and conditional Vangl2Δ/CD embryos displayed: i) a significant dilation in the diameter of renal tubules seen as an increased tubule cross-section area and a larger number of cells per cross-section; and ii) changes in cell shape indicative of defective AC. Surprisingly, post-natal mice showed virtually no difference in any of these aspects comparing to control mice, suggesting that other pathways may compensate for the lack of PCP signaling in maintenance of the tubule architecture. Limitations: a) The analysis of the renal tubules at the specific time points does not account for the dynamics of tubular movement and growth in real time; b) a mechanistic and morphological distinction between mice and humans may exist in the renal collecting duct tubules, pertaining to the Vangl2 gene’s influence in the PCP pathway; and c) the degree of mosaicism resulting from the gene excision by Cre-recombinase may correlate with the severity of the phenotype. Conclusion: We conclude that the PCP pathway is required for normal tubule development during embryogenesis. Our results, however, indicate that the cystogenesis seen in PKD postnatally may not be directly attributed to the disrupted PCP signaling, and requires the derangement of additional pathways.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".