Pierre Robin序列征 (Pierre Robin sequence, PRS)以先天性小颌畸形、舌后坠、腭裂为主要临床特征，目前对于PRS发病的分子机理认识有限。我们前期的研究发现：在小鼠神经嵴细胞中特异性敲除N-myc基因，其颅颌面表型类似PRS，本项目将通过以下研究内容阐明N-myc在PRS发生中的作用机制：①神经嵴细胞N-myc基因敲除对其自身、上皮细胞和迁移至舌的成肌祖细胞的行为有何影响以及对下颌发育的影响；②通过腭板、舌的体外培养实验，明确腭突上抬障碍和舌发育异常是由内在因素还是外在因素所致？③使用RNA-seq筛选差异表达基因，分析N-myc调控的靶基因，探讨不同来源细胞之间相互作用的分子机制；④在体外培养系统中操纵N-myc靶基因的表达，能否挽救表型？本研究将有助于我们认识N-myc在口腔颌面发育和PRS致病中的作用和分子机理。

Pierre Robin sequence (PRS) is characterized by congenital micrognathia, retrogression of tongue and cleft palate. At present, there is limited understanding of the molecular mechanism of PRS. Our previous studies have found that the specific knockout of N-myc gene in mouse neural crest cells is similar to PRS regarding the craniomaxillofacial phenotypes. This project will clarify the mechanism of the role of N-myc in PRS through the following research contents: ① How does the N-myc gene knockout in neural crest cells affect the behavior of themselves, epithelial cells and myogenic progenitor cells migrating to the tongue, and its impact on mandibular development? ② To investigate that the palatal process elevation disorder and tongue dysplasia are caused by internal or external factors by the in vitro organ culture experiments of palate and tongue. ③ To analyze target genes regulated by N-myc, and explore the molecular mechanism of interactions between cells from different sources by screening differentially expressed genes by RNA-seq. ④ To test whether the phenotypes can be rescued by manipulating the expression of N-myc target genes by in vitro organ culture system. This study will facilitate our understanding of the role of N-myc in oral craniofacial development and the pathogenesis of PRS.