Investigating the influence of the transcription factor Hindsight in a Notch-induced tumour model
Bibliographic record
Abstract
In Drosophila development, the adult salivary gland and hindgut are derived from populations of undifferentiated cells that are found in the larval stages and are known as the salivary gland imaginal ring (SGIR) and hindgut imaginal ring (HIR). The SGIR and HIR have recently been developed as models for tumourigenesis. In these tissues, the Notch signaling pathway normally regulates proliferation, whereas overactivation results in severe overproliferation. Upon further investigation of this tumour model, cells located at the boundary of the SGIR, and its neighbouring differentiated larval cells have been characterized as a polyploid transition zone (TZ) that is a hotspot for metastatic transformation (Yang et al., 2019; Wang et al., 2021). We report here that the zinc finger transcription factor Hindsight is expressed in the TZ cells of the SGIR as well as the most anterior cells of the HIR. In both of these contexts, ectopic expression of hnt throughout the imaginal rings is sufficient to suppress cell proliferation and promote cell growth through the endocycle. Moreover, such ectopic expression of hnt is also sufficient to completely suppress Notch-induced overproliferation in both the SGIR and HIR. Analysis of hnt somatic mosaics within the SGIR suggests that Hnt can function to regulate proliferation in a cell non-autonomous manner. Co-expression of the cell cycle regulator string and hnt resulted in a rescue of the hnt overexpression phenotype, consistent with a role of hnt in the downregulation of the expression of string. Interestingly, the overexpression of hnt in both the SGIR and HIR frequently resulted in apparent deposition of melanin, suggesting hnt overexpression is capable of inducing trans-differentiation whereby undifferentiated cells adopt the fate of melanin-producing crystal cells.
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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) | 0.001 | 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".