Inhibitory BMO signaling controls mammalian renal branching morphogenesis in vivo
Bibliographic record
Abstract
In this thesis I investigated the role of the inhibitory Bmp signaling pathway during mouse kidney renal development using (i) genetic haploinsufficiency models to investigate the functions of Bmp2 and Gpc3-Bmp2 interactions during renal development in vivo and (ii) conditional Alk3 loss-of-function in the UB lineage to investigate the function of Alk3-dependent Bmp signaling during RBM in vivo. During embryonic development, the collecting duct system of the kidney arises through iterative growth and branching of the ureteric bud (UB) and daughter collecting ducts, a process termed renal branching morphogenesis (RBM). Previous work in our lab identified an inhibitory ALK3-dependent BMP signaling pathway that controls cellular and morphogenetic events during RBM in vitro and in transgenic over-expression mouse models. However, the early embryonic lethality of homozygous Bmp2-/- and Alk3-/- mice has precluded complementary conventional loss-of-function studies to define the role of Bmp signaling during renal development in vivo. Results from this thesis provide the first genetic evidence that an inhibitory Bmp2 signaling pathway controls UB cell proliferation and branching during RBM in vivo, and that Bmp2 signaling is genetically modulated by Gpc3. Further, these results demonstrate an essential requirement of ALK3-dependent Bmp signaling for normal kidney development in vivo, and identify a critical architectural role for ALK3 in establishing and maintaining the primary UB branching pattern.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".