Genetic screen to identify novel potential regulators of dorsal closure in "Drosophila melanogaster"
Bibliographic record
Abstract
Dorsal closure of the Drosophila embryo represents the best characterized example of epithelial movement and fusion.This is due to the advanced genetics which allowed the identification of numerous genes that participate in dorsal closure.A deeper knowledge of the molecular mechanisms that drive dorsal closure leads also to a better understanding of other similar epithelial closure events such as wound healing and other processes that involve cell shape changes in general.The small Rho GTPases Drac1 and Dcdc42 are essential regulators of actin cytoskeleton dynamics and therefore are also key players in dorsal closure.To identify novel signaling components of Drac1 and Dcdc42 that potentially act during dorsal closure, we performed a genetic screen.To this end, we misexpressed dominant negative forms of either Drac1 or Dcdc42 (Drac1 N17 or Dcdc42 N17 ) specifically in the eye by using the Gal4/UAS-system.As a consequence, the resulting tester flies displayed eyes with a disrupted structure ("rough eye" phenotype) that was used as a starting point for a gain-of-function screen.Approximately 10'000 flies with random insertions of a UAS-containing enhancer promoter (EP) element were crossed to the Drac1 N17 or Dcdc42 N17 tester flies and the F1 generation was screened for modification of the rough eye phenotype.We selected modifiers that improved eye structure, i.e. suppressed the rough eye phenotype.Modification of the rough eye phenotype is supposed to be caused by EP dependent transcription of a nearby gene.These genes thus encode potential Drac or Dcdc42 signaling components.The decision to screen for eye (instead of dorsal closure) phenotype modifications was motivated, first, by the viability of the corresponding tester lines that made it possible to screen the F1 generation and, second, by the relative ease to examine the subtle eye phenotype modifications -to score for a partial suppression of the severe dorsal closure phenotypes caused by Drac1 N17 or Dcdc42 N17 embryonic overexpression was supposed to be too demanding and time consuming for this kind of large scale screening.This approach led to the identification of 17 genes, none of which has been previously reported to interact with Drac1 or Dcdc42.Their potential role in dorsal closure has not yet been investigated except for one suppressor gene: falafel.Loss-of-function mutations in falafel were generated that indeed resulted in various defects in dorsal closure besides other phenotypes.Thus this genetic approach identified at least one novel gene implicated in dorsal closure that probably would not have been picked up in conventional loss-of-function screens as its mutant phenotype is pleiotropic.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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 teacher head, 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".