Determining the Role of Extracellular Matrix Compliance on Facial Morphogenesis
Bibliographic record
Abstract
We have previously found that collagen 4 and laminin are thinner in regions of the frontonasal process undergoing growth, suggesting tissue compliance may contribute to regulation of facial morphogenesis. Lysyl oxidase (LOX) initiates enzymatic crosslinking of collagen and elastin. Crosslinking in extracellular matrix fibrils increases tissue stiffness and may constrain growth in certain directions while allowing cells to exert forces required for directional growth. Our goal was to examine the distribution of lysyl oxidase in the frontonasal process (FNP) of chick embryos during growth and fusion of the palate. At Hamburger and Hamilton stage 22, LOX is present in the ectodermal basement membrane along the FNP, but at stage 26 it is present primarily in the basement membrane lining the nasal pits. LOX is also present in the lateral edges of the mesenchyme of the FNP at stage 22, but is more present in the medial and caudal mesenchyme at stage 26. These results mirror the distribution of collagen 4 and laminin, where more crosslinking was observed in regions resisting growth (like the nasal pits) and in regions where cellular forces may be generated to direct growth (ectodermal basement membrane). We next prevented initiation of crosslinking with a small‐molecule from Lathyrus odoratus , beta‐aminoproprionitrile (BAPN), which permanently binds to LOX. Ingestion of L. odoratus causes osteolathyrism, a musculoskeletal degenerative disease, and researchers have found that BAPN administered in high concentrations to embryos causes skeletal and craniofacial deformities. We found that microinjections of BAPN in the caudo‐lateral edge of the FNP at low concentrations (50, 75, and 100 ng/uL) caused mild truncation of the FNP without affecting LOX localization or increasing cell apoptosis (via TUNEL staining). Together, these results provide preliminary evidence that tissue compliance may play an important role in facial morphogenesis. Future work will utilize a LOX RNAi vector to further examine the role of extracellular matrix crosslinking on palate growth and fusion. Support or Funding Information Funding was provided by: CIHR, and NIH, NIDCR R21‐DE028198
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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".