Regulation of Hippo signaling and planar cell polarity via distinct regions of the Fat intracellular domain
Bibliographic record
Abstract
The large Drosophila protocadherin Fat (Ft) is a receptor for signal transduction pathways that control growth (Hippo signaling), planar cell polarity (PCP), metabolism and the proximodistal patterning of appendages. The intracellular domain (ICD) of Ft is crucial in implementing its biological functions. Six regions of high conservation (named A-F) within the ICD have been identified, as well as distinct regions mediating Hippo pathway activity that have been functionally characterized via transgenic expression rescue assays. Here, we make targeted deletions of these highly conserved residues and the putative Hippo- and PCP-regulating domains of endogenous Ft using CRISPR/Cas9. Through transcriptomic, developmental and phenotypic analyses, we show that different regions of Ft contribute uniquely to chromatin dynamics, tissue morphogenesis, PCP and metabolic regulation. We also demonstrate that different regions of Ft regulate growth in opposite directions, with regions B and F promoting growth and region D inhibiting growth. Strikingly, conserved regions D and F are key regulators of the function of Ft in Hippo activity - exhibiting opposing effects on Hippo pathway modulation - and of the conserved regions, and D is the main regulator of PCP.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".