Regulation of Eye Growth and Development by the Lens

描述(申请人提供)：脊椎动物眼睛的发育和生长必须完全协调，才能将正确的视觉图像传输到大脑。晶状体在一定程度上负责协调眼睛的生长，但潜在的分子和细胞机制尚不清楚。我们将在墨西哥硬骨鱼中研究这个问题，这是一种硬骨鱼，由有眼的表层栖息形式(表层鱼)和盲穴居形式(穴居鱼)组成。眼原基最初是在洞鱼发育过程中形成的，但随后停止并退化，导致成年失明。首先退化的组织是晶状体。值得注意的是，将表层鱼的胚胎晶状体移植到洞穴鱼的视杯中，可以恢复成年洞穴鱼的完整眼睛。我们建议研究Astianax中调节眼睛生长和发育的晶状体的分子和细胞基础，这是唯一适合于晶状体操作的。前三个特定的目的是为了确定洞鱼视网膜、角膜和巩膜分化受阻的细胞事件，以及晶状体如何调节这些事件。在这些目标中，我们将结合晶状体移植方法和视网膜、角膜和巩膜发育的特定分子标记。第四个具体目标是识别编码影响眼睛其他部位发育的晶状体信号因子的候选基因。这些基因将通过使用从分离的表层鱼和洞穴鱼晶状体中获得的cdna文库进行消减杂交获得。第五个具体目标是确定候选基因在晶状体退化和其他眼睛组织的晶状体调节发育中的作用。这将通过功能丧失和功能获得研究，以及通过利用候选基因的特定属性来实现。我们期待这项研究为晶状体信号传递过程提供新的见解，并填补我们在理解眼睛正常和异常发育方面的一个主要空白。

DESCRIPTION (provided by applicant): The development and growth of the vertebrate eye must be perfectly coordinated in order to transmit correct visual images to the brain. The lens is responsible in part for coordinating eye growth but the underlying molecular and cellular mechanisms are unknown. We will investigate this problem in Astyanax mexicanus, a teleost species consisting of an eyed surface dwelling form (surface fish) and a blind cave-dwelling form (cavefish). Eye primordia are initially formed during cavefish development but subsequently arrest and degenerate, resulting in a blind adult. The first tissue to degenerate is the lens. Remarkably, transplanting a surface fish embryonic lens into a cavefish optic cup can restore a complete eye in adult cavefish. We propose to study the molecular and cellular basis of lens regulation of eye growth and development in Astyanax, which is uniquely suited for lens manipulations. The first three specific aims are designed to determine the cellular events underlying the arrest of retinal, corneal, and scleral differentiation in cavefish and how the lens modulates these events. In these aims we will combine lens transplantation methods with specific molecular markers for retina, cornea, and sclera development. The fourth specific aim is to identify candidate genes encoding lens-signaling factors affecting the development of other eye parts. The genes will be obtained by a subtractive hybridization using cDNA libraries obtained from isolated surface fish and cavefish lenses. The fifth specific aim is to determine the role of the candidate genes in lens degeneration and lens-regulated development of other eye tissues. This will be done by loss-of-function and gain of function studies, as well as by capitalizing on specific properties of the candidate genes. We expect this research to provide new insights into lens signaling processes and fill a major gap in our understanding of both normal and abnormal eye development.