Hypertelorism of <i>Efnb1</i> Null Mice Occurs Independently of Changes to Underlying Brain Shape
Bibliographic record
Abstract
Efnb1 +/− heterozygous mice phenocopy many craniofacial characteristics of craniofrontonasal syndrome (CFNS), a disorder caused by heterozygous EFNB1 loss of function mutations. Because ephrin‐B1 is expressed strongly throughout the developing telencephalon in mice, we hypothesized that hypertelorism (increased distance between the eyes) in Efnb1 +/− mice could be secondary to early changes in the form of the underlying cerebral cortex. This stems from the common expectation that intramembranously ossified bones surrounding the brain can accommodate unusual patterns of brain growth. We quantified the effect of the heterozygous null mutation on early facial and brain morphology from computed tomography (CT) images of iodine stained E14.5 Efnb1 +/− (n=17) and control embryos (n=18). Facial size and shape were measured from manually placed landmarks using geometric morphometrics. Differences in general and local brain size were quantified across soft tissue contrasted CT image volumes using Jacobian determinants derived from the nonlinear registrations required align all specimen images. This analysis indicated that major portions of the forebrain, midbrain, and hindbrain are reduced in size in Efnb1 +/− embryos compared with controls. After accounting for differences in overall brain size, we noted a particularly strong local reduction in the subpallium of the forebrain (progenitor of the basal ganglia). To test whether facial changes were secondary to brain dysmorphology in Efnb1 +/− mice, we measured facial shape from CT images of unstained E14.5 embryo controls (n=20), embryos with conditional expression in neural crest derived facial tissues ( Efnb1 lox/+ ; Sox10 Cre − ) (n=10), and in neural tissues including the telencephalon ( Efnb1 lox/+ ; Sox1 Cre ) (n=10). Although brain size changes are evident in Efnb1 +/ − , there is no facial shape dysmorphology in mice with neural tissue specific Efnb1 heterozygosity. However, the facial dysmorphology in mice with neural crest Efnb1 heterozygosity are similar in direction and strength to the dysmorphology noted within the Efnb1 +/ − mice. Our results indicate that strong facial dysmorphology in Efnb1 +/ − mice is the primary result of heterozygous expression within neural crest‐derived facial tissues. While brain‐skull tissue interactions are critical during development, we should not necessarily assume that skull dysmorphology is secondary when both are affected. Support or Funding Information This work is supported by the NIH/NIDCR R01DE023337 and Stony Brook University startup funds to CJP. 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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".