Golgb1 in Craniofacial Development

腭裂是一种常见的重大出生缺陷，需要手术干预短期内 出生后，并对受影响的个人有重大的长期健康影响。 尽管在分子生物学的理解上已经取得了巨大的进展， 在过去的二十年中，腭发育的调节，目前已知的遗传 原因占不到20%的人类腭裂病理。通过 表型驱动的诱变筛选和全外显子组测序分析，我们有 在一个新的腭裂突变体中发现了Golgb1基因的功能缺失突变 小鼠品系。Golgb1编码定位于高尔基体的大型跨膜蛋白 设备.尽管一些人类发育障碍与 高尔基体相关蛋白的突变，很少有研究表明高尔基体的作用 以及高尔基体相关蛋白在发育和器官发生中的作用。本课题 将产生携带Golgb1独立基因靶向突变的小鼠，以证实 Golgb1的功能缺失会导致腭裂我们将识别特定的细胞， 分子和形态发生过程中的腭发育， Golgb1函数。这些研究将为分子和细胞生物学提供新的见解。 腭发育机制和颅面分娩的致病机制 缺陷

Cleft palate is a common major birth defect that requires surgical intervention shortly after birth and has significant long-term health implications for the affected individuals. Although there has been tremendous progress in the understanding of molecular regulation of palate development in the last twenty years, currently known genetic causes account for less than 20% of cleft palate pathology in humans. Through a phenotype-driven mutagenesis screen and whole exome sequencing analyses, we have identified a loss-of-function mutation in the Golgb1 gene in a new cleft palate mutant mouse strain. Golgb1 encodes a large transmembrane protein localized to the Golgi apparatus. Although several human developmental disorders have been associated with mutations in Golgi-associated proteins, few studies have characterized the roles of Golgi and Golgi-associated proteins in development and organogenesis. In this project, we will generate mice carrying an independent gene-targeted mutation in Golgb1 to confirm that loss of function of Golgb1 causes cleft palate. We will identify specific cellular, molecular, and morphogenetic processes during palate development that depend on Golgb1 function. These studies will provide novel insights into the molecular and cellular mechanisms of palate development and pathogenic mechanisms of craniofacial birth defects.