Bibliographic record
Abstract
We are interested in developmental morphodynamics and the ability of muscle to provide mechanical cues for organogenesis during development. Our study of compound mouse knockout (Myf5 −/− :MyoD −/ ) embryos that entirely lack skeletal musculature has revealed that these embryos develop abnormal phenotypes in many organs, such as skeleton (palate, mandible, clavicle), lungs, retina and inner ear. In this study we analyzed the altered development of the mouse inner ear and its sensory fields. Amyogenic fetuses lack skeletal muscles that move the chain of three middle ear ossicles responsible for the transfer of sound vibrations. They are also unable to tilt their head which prevents the perception of angular acceleration. The inner ear areas that were most affected in amyogenic embryos were vestibular sensory fields, i.e., cristae ampullaris, sensitive to angular acceleration. Our finding that a specific vestibular hair cell type 1 was absent in mutants was further used to identify a profile of genes specific for the lacking cell type. We performed a DNA microarray analysis to compare gene expression between inner ear sensory fields of amyogenic and wild type mouse embryos. This analysis generated a list of 10 up‐ and 87 down‐regulated genes in mutant inner ear tissues. We subsequently performed a detailed consultation of web‐accessible mouse databases regarding the genes with altered expression in mutants. This allowed us to identify 6 candidate genes with a possible role in the development of the inner ear sensory organs: Actc1, Pgam2, Ldb3, Eno3, Hspb7 and Smpx. They were established as candidate genes based on their altered expression in our mutant embryos compared to the wild type, as well as their previously documented expression in the sensory organs of the mouse inner ear. Further analysis of inner ear tissues of knockout embryos for these specific molecules is necessary to confirm, or rule out, the role of candidate genes in the inner ear development. Additionally, we searched for human homologues of the candidate genes since a number of syndromes in humans have inner ear abnormalities associated with them. Mutations in one of our candidate genes, Smpx, have been reported as the cause of X‐linked deafness in humans. Our current study suggests an epigenetic role that skeletal muscle might play in organogenesis, and offers an approach to finding novel genes responsible for altered morphology in the inner ear. Support or Funding Information Natural Sciences and Engineering Research Council of Canada Canada Foundation for Innovation
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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".