我们前期研究发现Dlx2过表达可引起小鼠神经管裂开、面裂和脊柱裂开、脊柱弯曲畸形。其颅颌面畸形的发生与颅神经嵴细胞增殖降低而凋亡增加、成软骨分化增强而成骨分化发生障碍有关。此外，Dlx2过表达可引起Fgf9和p53表达发生改变，以往研究表明Fgf9对颅神经嵴细胞骨/软骨向分化有重要影响，而p53主要调控细胞的增殖和凋亡，提示Fgf9和p53可能参与Dlx2过表达引起颅神经嵴细胞增殖、凋亡和分化异常。本研究以前期建立的Dlx2在神经嵴细胞特异性过表达转基因小鼠模型为基础，应用鳃弓器官体外培养、颅神经嵴细胞培养、病毒转染、RNA干扰、生物信息学分析和启动子点突变等技术，研究Dlx2、Fgf9和p53在调控颅神经嵴细胞发育中的相互作用及分子机制，探索Fgf9基因治疗和p53药物抑制在挽救Dlx2过表达引起的先天性颅颌面畸形中的药物投递方案及可行性，有望为临床上预防和诊治相关疾病提供一定理论基础。

Our previous study revealed that Dlx2 over-expression could lead to neural tube defect, mid-facial cleft and spinal deformity, and these craniofacial deformities may due to the decreased cell proliferation, increased cell apoptosis, abnormal chondrogenesis and impaired osteogenesis within the cranial neural crest cell (CNCCs) population. Additionally, Dlx2 over-expression could up-regulate the expression of Fgf9 and p53, and previous studies demonstrated that Fgf9 plays crucial roles in the chondrogenic and osteogeneic differentiation of CNCCs, whereas p53 mainly regulate the cell proliferation and apoptosis. All of above finds imply that Fgf9 and p53 may be involved in abnormal proliferation, apoptosis and differentiation of CNCCs induced by Dlx2 over-expression. In this study, based on the transgenic mouse model for neural crest cell specific Dlx2 over-expression, we will try to study the interactions and molecular mechanisms between Dlx2, Fgf9 and p53 during CNCCs development by using organ culture, cell culture, virus transfection, RNA interference, bioinformatic analysis and promoter point mutation, etc, and to find out the suitable drug delivery methods for Fgf9 gene therapy and pharmacological inhibition of p53 to rescue the Dlx2 over-expression induced craniofacial deformities, which will be useful for prevention, diagnosis and treatment for these craniofacial deformities.