Understanding the mechanism of vision development.

视网膜发育是一个动态的过程，从子宫开始，出生后一直持续到13岁。由于多种因素的影响，斑马鱼是研究视觉发育的最佳模式生物。斑马鱼视网膜的解剖、发育和生理特征与人类相似。到受精后72小时，视网膜的形态和功能像成年人一样健壮，并可通过视觉行为分析进行测试。在这个项目中，我们将使用基于CRISPR-Cas9的技术来操纵基因，这些基因将改变斑马鱼的视动反射，并将其与视网膜结构和功能相关联。我们将分析与视力发育相关的基因组广泛关联研究(GWAS)的汇总统计数据，以确定斑马鱼基因靶标的优先顺序。在并列动物存在的情况下，将实施双重敲除策略来探索斑马鱼的基因冗余以及潜在的亚功能或新功能方面。此外，我们将利用深度学习技术开发创新的视觉行为分析工具。这些工具的设计是多才多艺的，适用于各种实验室环境，允许刺激和获取独立。虽然以前的工作已经证明使用视动反射作为一种强有力的测试方法来测量视觉行为，但目前还没有报告标准。我们将系统地开发一种使用不同刺激范围的斑马鱼视动反射检测的最佳方案，目的是在这一领域建立报告标准。这种有针对性的方法不仅将确保该领域新的方法学进步，而且还将提高我们对正常视觉发育和相关基因调控网络机制的理解。

Retinal development is a dynamic process that begins in utero and continues postnatally up to the age of 13 years. Zebrafish are the best choice of model organism to study vision development due to multiple factors. Zebrafish retinal anatomy, development and physiological characteristics are like humans. By 72 hours post-fertilisation retinal morphology and function is robust like adults and testable using visual behaviour assays. In this project we will use CRISPR-Cas9 based techniques to manipulate genes that will modify the optokinetic reflex and correlate this to retinal structure and function in zebrafish. We will analyse summary statistics from Genome Wide Association Studies (GWAS) related to vision development to prioritise gene targets in zebrafish. In cases where paralogs are present, a double knockout strategy will be implemented to explore gene redundancies, as well as potential sub- or neo-functional aspects in zebrafish. Additionally, we will develop innovative visual behaviour analysis tools using deep learning techniques. These tools are designed to be versatile and applicable across various laboratory settings, allowing for stimulus and acquisition independence. Whilst previous work has demonstrated the use of the optokinetic reflex as a robust assay to measure visual behaviour, currently no reporting standards exist. We will systematically develop an optimal protocol for optokinetic reflex assay in zebrafish using range of different stimuli with the aim of creating reporting standards in this domain. This targeted approach will not only ensure novel methodological advances in the field but also improve our understanding on the mechanisms of normal vision development and associated gene regulatory networks.