Extracellular Matrix Composition Is Altered Alongside Dysmorphology in the Developing Palate
Bibliographic record
Abstract
Normal morphogenesis of the primary palate involves directed outgrowth of the facial primordia until they meet and fuse. Gradients of cellular proliferation induced by growth factors are the current paradigm for directed outgrowth, but active cellular migration and physical force propagated through the extracellular matrix (ECM) likely also direct growth. Previously we showed that two of the main components of the ECM, collagen IV and laminin, are thinner in regions of the frontonasal process (FNP) undergoing growth, suggesting tissue stiffness may passively constrain growth in certain directions. We have also shown that increasing Fibroblast growth factor (FGF) signaling in the FNP of chick embryos prior to palate fusion caused overgrowth and disrupted cellular organization. Since cells form and modify the ECM, and since the ECM is required for cellular organization and movement, the effects of FGF signaling on morphogenesis may be due in part to active feedback between ECM and cells. Our goal was to examine the changes to the ECM in the FNP following alteration of FGF signaling. Blocking FGF signaling with SU5402 caused hypoplasia of the FNP and increased the concentration of collagen IV and laminin in regions of expected outgrowth. Conversely, increasing FGF signaling with exogenous FGF2 caused overgrowth of the FNP and decreased concentration of the ECM components. Analysis using transmission electron microscopy of the FGF2 treated samples suggests increasing FGF signaling also decreases the thickness of the epithelium and basement membrane. These results provide preliminary evidence that ECM may play an important role in facial morphogenesis, and that FGF signaling may affect an active biomechanical feedback system between cells and ECM. In the future I will further characterize ECM composition and compliance across the FNP using Fourier transform infrared spectroscopy and atomic force microscopy to generate 3‐dimensional maps of biomechanical properties in the face. I will also use confocal microscopy to map cellular organization across the face. I will overlay these maps onto representative reconstructions of the face to correlate regional variation in biomechanical properties and cellular organization with dysmorphologies that occur following exogenous modulation of FGF signaling.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".