Insertional mutagenesis and ear development

发育基因组学组一直在使用斑马鱼遗传学和分子胚胎学的结合来研究耳朵和听力的发育。我们把注意力集中在斑马鱼胚胎致死性突变筛选中分离的几条细胞系的研究上。其中两个突变引起了特别的兴趣。首先是叉头相关转录因子Foxi1的突变。这种突变在颌骨的形成和发育上都有缺陷。我们正在研究这种转录因子的功能机制，并开始在感觉基板发育和颅面元件形成之间建立联系。我们正在研究的第二种突变涉及一种名为claudinJ的紧密连接蛋白的破坏。这种基因的突变会导致斑马鱼胚胎的耳聋和前庭功能缺陷。我们正试图确定这是如何发生的。该实验室的另一个重点是开发用于研究基因组范围内基因表达的工具。我们直接参与了斑马鱼基因寡基微阵列的开发。我们也在致力于开发斑马鱼插入突变图谱的冷冻库，以便分离出特定的基因破坏。

The Developmental Genomics Section has been using a combination of zebrafish genetics and molecular embryology to study ear and hearing development. We have focused our attention on the study of several lines isolated in a screen for embryonically lethal mutations in zebrafish. Two of these mutations have been of particular interest. The first is a mutation in the forkhead related transcription factor Foxi1. This mutation has defects in both otic placode formation and jaw development. We are studying the mechanism of function for this transcription factor and are beginning to create a connection between sensory placode development and the formation of craniofacial elements. A second mutation that we are studying involves the disruption of a tight junction protein called claudinJ. Mutations in this gene cause deafness and vestibular defects in zebrafish embryos. We are trying to determine how this occurs. Another focus of the lab is to develop tools for studying gene expression on a genome wide scale. We have been directly involved in the development of an oligo-based microarray for zebrafish genes. We are also working on developing a frozen bank of mapped zebrafish insertional mutations allowing for the isolation of a specific gene disruption.