Examining the Correlation Between Cellular and Gross Morphological Changes In the Developing Mouse Skull
Notice bibliographique
Résumé
INTRODUCTION The mammalian skull develops from intramembranous and endochondral ossification. Thus, differentiation and proliferation of osteoblasts and chondrocytes play an integral role in skull development and the resulting morphology. While this connection between cellular behaviour and morphology is intuitive, the relationship between changes at the cellular level and gross phenotypic changes in the skull are still poorly understood. In this study we ask: How do changes in osteoblast and chondrocyte differentiation and proliferation within facial sutures and cranial base synchondroses affect the gross morphology of the mouse skull? We use a mutant mouse model (Cx43 I130T/+ ) wherein the GJA1 gene encoding for the gap junctional protein Connexin43 has been mutated, reducing gap junctional conductance by 50%. Cx43 is critical in bone development, and is known to stimulate osteoblast differentiation. Presently, the literature is vague surrounding the effects of Cx43 on chondrocytes. Cx43 I130T/+ mice display craniofacial anomalies, such as smaller facial bones, elongated nasal cartilages and microcephaly. Preliminary data from our lab shows that the cranial base is also altered in Cx43 I130T/+ adult mice. We predict that these morphological changes in the face and cranial base will be mirrored by altered cellular behaviour in the facial sutures and cranial base synchondroses. METHODS Skulls of P0 Cx43 I130T/+ mice and their wildtype (WT) littermates were imaged using μ‐CT. Three‐dimensional landmarks were collected from scans and differences in shape were analyzed using geometric morphometrics. Paraffin sections were taken from skulls of each genotype and stained for histomorphometry and markers of cell proliferation and osteoblast and chondrocyte differentiation. Measures of cell density were collected for facial sutures and cranial base synchondroses and compared between groups. RESULTS While we found no significant differences in skull size between genotypes, we did find significant shape differences. Mutant mice have proportionately smaller facial bones and orbits and relatively larger basicrania compared to WT mice. Mutant skulls are also severely under‐mineralized. There is no difference in osterix‐positive cell density in facial sutures between groups, but we did find an altered pattern of osteocalcin expression in mutant facial sutures. Total area of each synchondrosis is similar for both genotypes, but there are significant differences in resting zone area of each synchondrosis between groups. Cell density of Sox9‐positive cells within the synchondroses are the same for mutant and WT mice. CONCLUSIONS Our shape analyses indicate that the morphological changes observed in adult Cx43 I130T/+ mice are present at birth. While we did find some differences in osteoblast and chondrocyte profiles between groups, the link between cellular changes at the tissue level and gross phenotypic changes is not straightforward. Support or Funding Information This work is supported by NSERC. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,002 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».