颅颌面畸形是发生率最高的出生缺陷，尤以腭裂最为常见。上腭由前端硬腭和后端软腭构成，对其模式化和转录调控机制所知甚少。Hox转录因子作为常见组织特异性的辅助因子，指导器官的模式特化。然而，在上腭中并不表达Hox，是哪些转录因子决定了上腭的前后硬腭和软腭的模式形成还是未知之迷。同源框基因Shox2在前腭特异性地表达，其突变导致前腭裂，且硬腭骨量大幅减少，表明其在上腭模式化和骨发生中具有重要功能。前期研究表明，Shox2可能作为核心转录因子，与其他转录因子和染色质重塑蛋白共同作用，形成转录复合物，结合到特定的增强子上，调控硬腭的模式化及骨发生。将采用遗传、分子生物学、基因组学及生物信息学手段，进行深入研究，进一步理解上腭发育及腭裂发生的机制，对进一步理解颅颌面其他器官模式形成和骨发生机制也将有重要的启迪。

Cleft palate represents one of the most frequently occurred human birth defects. The mammalian palate is anatomically divided into the anterior bony hard palate and the posterior muscular soft palate. However, how the anterior hard palate is patterned and how the palatal osteogenesis is controlled remains unknown. Hox genes encode homeodomain-containing transcription factors that determine the pattern of organ development. However, In the Hox-free developing palate, this raises a fundamental question as what transcription factors to specify and pattern the hard and soft palate. The homeobox gene Shox2 is expressed specifically in the anterior palatal mesenchyme, overlapping with the future bony hard palate domain. We have shown previously that Shox2 mutation leads to not only a rare type anterior clefting of the secondary palate, but most intriguingly, also the significantly reduced bone formation in the hard palate, indicates an essential role for Shox2 in organ patterning and skeletogensis. Our preliminary studies present evidence that Shox2 may interact with other transcription factors and chromatin remodeling factors to ground the patterning and skeletogensis of hard palate. In this application, we will employ genetics, biochemistry, molecular biology, genomics and bioinformatics approaches to explore the molecular patterning of the hard palate. The results obtained will provide novel knowledge for understanding of palate development and cleft palate formation and provide solid foundation for future tissue engineering of palatal bone for clinical treatment/repair of cleft palate defects.