Loss of planar cell polarity gene fuzzy leads to defective branching morphogenesis and cystogenesis in embryonic kidneys
Bibliographic record
Abstract
Abstract (English)Background: The PCP effector gene Fuzzy is essential for organogenesis. In Drosophila, it is critical for establishing planar cell polarity via controlling the actin cytoskeleton. In vertebrates, the role of Fuzzy is less clear, but it appears to control some aspects of trafficking protein cargos to the basal body. Fuzzy has been designated as a ciliogenesis and planar polarity effector (CPLANE) gene. Disruption of Fuzzy in mice results in severe malformations, including neural tube defects, polydactyly, facial defects, etc, suggesting its participation in various signaling pathways.Methods: To study kidney development, homozygous E14.5 and E16.5 embryos carrying a gene-trap Fuzzy mutation and wildtype (control) littermates were harvested for immunofluorescense and in situ hybridization (ISH) studies.Results: Fuzzy-/- embryos exhibited profound renal hypoplasia at E14.5. Although SIX2+ progenitor cells and their differentiation were unaffected, the number of the ureteric buds (UB) was decreased to 50% of control. This was accompanied by a ~ 50% reduction in the number of glomeruli without a decrease in the number of podocytes per glomerulus. ISH studies indicated that Gdnf expression was unaffected, while UB specific markers Ret, Wnt11 were expressed in Fuzzy-/- kidneys at the levels comparable to control animals. The level of the Hippo kinase pathway effector YAP was decreased significantly in UBs. At E16.5, Fuzzy-/- embryos exhibited glomerular cysts in the medullary layer, manifested by the dilation of Bowman’s capsule. E16.5 Fuzzy-/- embryos also developed proximal tubular cysts but collecting ducts remained intact. The renal cysts were associated with defective ciliogenesis. Cilia length in Fuzzy-/- was half of that in the control animals. Conclusions: Our study demonstrates that the impaired UB branching is a major cause of renal hypoplasia in E14.5 Fuzzy-/- embryos and is associated with a decreased proliferation rate and a decrease in Yap expression in the UBs. Loss of Fuzzy leads to glomerular and proximal tubular cysts, which are associated with the defective ciliogenesis. Thus Fuzzy plays a crucial role during kidney development and acts via impacting Wnt, Sonic hedgehog (Shh) and Hippo kinase signaling 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) | 0.000 | 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) | 0.004 | 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".