颌面形态是由骨骼肌肉系统所决定，但由于颌面肌肉尤其是连接其与骨骼的肌腱发育模式与分子调控研究缺乏，使得颌面先天发育畸形机制研究多局限于骨发育自身。课题组在对Osr2-cre;Rosa-fgf8小鼠研究中发现Fgf8仅在咬肌肌腱被特异性激活而致肌腱分化障碍，却出现咬肌退化与下颌明显短缩，这强烈提示咬肌肌腱发育对下颌骨形态形成具有重要作用。本项目拟构建与利用肌腱特异性Cre工具小鼠，探明颌面肌腱发育模式及FGF信号通路等关键调控分子的作用机制；继而以上述模型咬肌与肌腱连接结构的精细组装与分子调控为切入点研究颌面肌肉与肌腱相互作用; 最后利用Hippo通路条件性基因敲除小鼠辅以三维重建技术，探明咬肌收缩力传导及肌腱特异性蛋白对下颌骨大小形态及其表面次生结构形成的作用。本项目将通过系统研究咬肌肌腱发育模式及咬肌-肌腱-下颌骨相互作用的分子调控，为颌面发育畸形病因研究与再生修复提供新的科学依据。

Craniofacial morphology is determined by the musculoskeletal systems, however, there are very few studies on the development and molecular regulation of craniofacial muscles, especially the tendon, restricting the insights on craniofacial deformity only to the skeleton. Our latest research found that when Fgf8 was specifically activated in the developing masseter tendon of Osr2-cre;Rosa-fgf8 mouse embryos, not only the tendon differentiation was impaired, but also the masseter regressed and the mandibular bone shortened. These findings strongly suggested that masseter tendon development was indispensable for the mandibular morphology. Therefore, we plan to generate and utilize the tendon specific Cre mouse line to investigate the craniofacial tendon development and the role of FGF signaling in the processes. Then, we will explore the interactions between craniofacial muscle and tendon by exploiting the precise structure and molecular regulation in the junction of masseter and tendon on the above mouse models. Finally, by applying 3D image reconstruction and the conditional knock-in mice of Hippo signaling, we will address the roles of masseter contraction and tendon specific proteins in the formation of mandible morphology and secondary structures. Our study will disclose the molecular regulation on masseter tendon development and masseter-tendon-mandible interactions, which will provide scientific basis for the etiology, regeneration and repair of craniofacial deformity.