眼球发育异常导致视觉器官结构畸形，严重影响视功能，是儿童致盲的主要原因。组蛋白乙酰化酶Hdac8为黏连蛋白复合物的关键调控因子，以往研究显示Hdac8基因是多发性先天发育异常，即德朗热综合症的重要致病基因，可导致眼球及多种器官发育异常，但未见其影响眼球发育的相关机制报道。我们前期对伴有眼部症状的德朗热综合症患者外显子组测序，鉴定了新的Hdac8突变位点；前期研究显示斑马鱼Hdac8氨基酸序列与人高度同源，并通过原位杂交技术发现斑马鱼受精后24小时阶段Hdac8基因在眼和后脑部分有强表达。因此，本项目拟以斑马鱼为模型，应用分子遗传学研究方法，探索Hdac8基因在早期胚胎和眼球发育中的表达模式，鉴定Hdac8敲除或mRNA过表达后的眼部表型，寻找其下游靶基因和作用位点，从而深入研究Hdac8基因在眼球发育中的生理功能及其作用的可能分子机制，以期从新的角度和内容阐述眼球发育异常的遗传与分子机制。

The abnormal development of eyes leads to congenital structural changes and visual disturbance, which is one of the major causes of children blindness. Histone acetyltransferase Hdac8 is a key regulation factor of cohesin. Recent studies documented that mutations in Hdac8 cause Cornelia de Lange Syndrome, which shows up as multiple organs system abnormalities including eye dysplasia. However, the function and mechanism of Hdac8 on eye development remain elusive. By exome sequencing, we determined a new missense mutation of Hdac8 in Cornelia de Lange Syndrome with eye dysplasia. The zebrafish Hdac8 share similarity with human, and the gene is expressed at high level at 24hpf (hours-post-fertilization) in zebrafish eyes. By using the well established zebrafish system, we will explore the early expression of Hdac8, analyze the phenotype caused by Hdac8 knockdown and mRNA over expression, and its down stream effectors. The project will elucidate the function and mechanism of Hdac8 during eye development and provide new insights into the prediction and prevention of eye dysplasia caused by Hdac8.