Emergent Properties of Facial Morphogenesis Regulated by Fgf Signaling
Bibliographic record
Abstract
Craniosynostosis is a severe disorder that may be caused by activating mutations in Fibroblast growth factor receptors (FgfRs) that affects development of the skull and is characterized by premature fusion of the cranial sutures. In addition to dysmorphology of the skull, affected individuals also have facial dysmorphology. We have previously used an avian model to explore the role that a disease‐causing allele of FgfR2 (FgfR2 C278F ) plays in producing malformations of the middle and upper face at early stages of development. In that work we observed a wider midface, which resembles what is observed in human patients, and this was directly related to decreased cell proliferation and a disrupted net polarization of the mesenchymal cells in the growing facial primordia. We have extended this work by examining the role of the Map kinase, PLC‐gamma, and PI3K pathways downstream of Fgf signaling in producing facial dysmorphology, as well as directly blocking FgfR activation. We implanted beads soaked in small molecular inhibitors (MEK1/2: U0126, PLC‐gamma: U‐73122, PI3K: LY 294002, FgfR activation: SU5402) into the right side of the developing avian face at HH22 and examined morphological and cellular outcomes at various times of development. First, we determined that each inhibitor substantially and specifically down‐regulated its respective pathway using immunohistochemistry to assess expression of down‐stream targets of activation of each pathway. We then determined that each pathway significantly reduced cell proliferation and altered cell polarization in the mesenchyme. Blocking each pathway also created severe craniofacial malformations that were observed at early and late time points. There are many inputs to each of these pathways, and our data suggest that each participate in regulation of a similar set of cellular processes that contribute to the emergence of morphogenetic processes in facial development. Support or Funding Information NIH: R01DE019638, R01DE018234, R21DE028198 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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".