Epithelial cell shape changes contribute to regulation of ureteric bud branching morphogenesis
Bibliographic record
Abstract
Branching morphogenesis orchestrates organogenesis in many tissues, including the kidney, where ureteric bud (UB) branching determines kidney size and shape and the final nephron number. Molecular regulation of UB branching is rather well studied, whereas the cellular mechanisms and tissue organization during UB arborization are less understood. Here, we characterized epithelial cell morphology in three dimensions (3D), studied mechanisms regulating cell shape changes, and analyzed their contribution to novel branch initiation in normal and branching-incompetent bud tips. Unbiased machine-learning-based segmentation of tip epithelia identified geometrical round-to-elliptical transformation as a key cellular mechanism facilitating growth direction changes to gain optimal branching complexity. Cell shape and molecular analyses in branching-incompetent epithelia demonstrated a distinct failure to condense cell size and modify its conformation. This, together with changes in adhesive forces, defective actin dynamics, and disorganization in myosin-9 (MYH9)-based microtubules, suggests altered biophysical properties in tip cells, where branch point decisions are made and actualized. The data demonstrate that dynamic changes in volume and morphology of individual epithelial cells, together with optimal traction stress, facilitate novel branch formation in the UB tip niche. Based on these results, we propose a model where epithelial cell crowding, in tandem with stretching, transforms individual cells into elliptical and elongated shapes. This creates local curvatures that drive new branch formation during the ampulla-to-asymmetric ampulla transition of the UB.
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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 | 0.001 | 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".