Role of planar cell polarity gene vangl2 in kidney development and disease
Bibliographic record
Abstract
The Planar Cell Polarity (PCP) signaling pathway is crucial for tissue morphogenesis.Vangl2 protein is central in the PCP pathway: its loss is embryonic lethal causing neural tube defects in mice and humans.In the kidney, PCP signaling is thought to be important for the organization of glomerular epithelial cells, podocytes, along the glomerular basement membrane.Podocyte cell protrusions, foot processes (FPs), are critical for kidney filtration functions; loss of FP architecture results in proteinuria and, in severe cases, focal segmental glomerulosclerosis (FSGS).Additionally, an effect of PCP pathway on podocyte shape, actin rearrangement and cell motility was previously described.We, therefore, hypothesized that the PCP pathway may be critical for glomerular development and function.We first characterized the Vangl2 expression pattern in developing mouse kidneys and showed that Vangl2 is dynamically expressed in developing glomeruli.To examine whether loss of Vangl2 affects podocyte differentiation and glomerular functions, we created a conditional podocyte-specific Vangl2 knockout mouse (V2-POD).V2-POD E17.5 embryos exhibit a delayed maturation of glomeruli compared with controls.In adult mice, we detected significantly smaller glomeruli, yet filtration functions remained unaffected.However, when challenged with a nephrotoxic agent, V2-POD mice displayed an exacerbated degree of both acute and long-term glomerular injury indicating a function of Vangl2 in both glomerular development and disease (described in Chapter 2).To ascertain the mechanism behind PCP signaling in podocytes, we used both in vivo and in vitro settings (described in Chapter 3).In a Looptail mouse with a ubiquitous germline mutation of Vangl2 gene, we detected a profound disruption of renal morphology and V. GLOMERULAR DYSFUNCTION: 37 Introduction to Glomerular Disease: 37 Genetic causes of nephrotic syndrome: 38
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".