Bazooka and atypical Protein Kinase C regulate dynamic actomyosin networks during Drosophila amnioserosa apical constriction
Bibliographic record
Abstract
Cell shape changes drive tissue remodeling. Polarized activity of actin and myosin drive apical constriction, as seen for example in Drosophila embryonic amnioserosa cells during dorsal closure (DC). My first aim was to characterize interactions between apical actomyosin networks and the cell polarity regulators Bazooka (Baz, the Drosophila Par-3), Par-6, and atypical Protein Kinase C (aPKC) (the PAR complex) during Drosophila DC. I found that both actomyosin networks and the PAR complex are enriched at the apical surfaces of amnioserosa cells and that actomyosin contractility is driven by cyclical assembly and disassembly of actomyosin networks. The pulsatile actomyosin networks translocate across persistent apical surface PAR complex puncta. To assess whether the PAR complex interacts with actomyosin, I characterized myosin dynamics with PAR loss- and gain-of-function perturbations. Baz enhances, whereas Par6/aPKC inhibits actomyosin. These studies suggest that PAR proteins regulate pulsatile apical actomyosin networks mediating constriction of amnioserosa cells. My next aim was to characterize actomyosin networks during a shift in their dynamics. Amnioserosa constriction transitions from pulsatile to persistent from early to late DC. Since oscillatory networks result from delayed negative feedback, I examined whether such regulation exists in these actomyosin networks. The actomyosin inhibitor aPKC is recruited to the apical surface by actomyosin and, in turn, aPKC recruits Baz. To examine the significance of Baz – aPKC dynamic interactions, I ectopically stabilized their interactions. This served to inhibit the antagonism of actomyosin networks by aPKC, suggesting that Baz can act as a competitive inhibitor of aPKC. I found that interactions between Par-6 and Baz increase during DC, suggesting an increase in aPKC inhibition during DC progression. To examine whether decreased inhibition can tune oscillatory actomyosin networks, we collaborated with Qiming Wang and Dr. James Feng (University of British Columbia) to test this oscillation in silico. Computer modeling suggests that decreasing delayed negative feedback can transition actomyosin oscillations towards stabilized constriction. Together, these results demonstrate the requirement of Baz – aPKC interactions for their localization and for dynamic regulation of aPKC by a competitive inhibitor. Finally, my research reveals a regulatory circuit to tune actomyosin behaviour during development.
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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) | 0.001 | 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".