Biomechanical strain patterns in Meckel's cartilage underlie mandibular variation in FGFR2 mouse models

Sequence variations in fibroblast growth factor receptor 2 (FGFR2) are associated with craniosynostosis syndromes, disrupting craniofacial development, yet early mandibular alterations remain poorly characterized. This study examined Meckel's cartilage (MC) and mandibular morphology in mouse models of Apert (Fgfr2^+/P253R) and Crouzon (Fgfr2c^C342Y/+) syndromes using Euclidean distance matrix analysis and finite element modeling at embryonic days 14.5 and 16.5. Apert mice exhibited significant MC shortening and elevated, widespread strain in the growth center area correlating with mandibular shortening and asymmetry. In contrast, Crouzon mice showed minor MC changes and localized strain peaks with larger mandibles. These biomechanical perturbations in Meckel's cartilage are associated with distinct mandibular phenotypes, consistent with a bidirectional relationship in which altered strain environments may both influence and reflect mandibular dysmorphogenesis during early development. The findings enhance our understanding of the biomechanical basis of mandibular anomalies associated with FGFR2 mutations, informing future investigations into craniofacial morphogenesis.