Regulation of Eye Growth and Development by the Lens

描述（由申请人提供）：脊椎动物眼睛的发育和生长必须完全协调，以便将正确的视觉图像传输到大脑。透镜部分负责协调眼睛的生长，但其潜在的分子和细胞机制尚不清楚。我们将在Astyanax mexicanus中调查这个问题，Astyanax mexicanus是一种硬骨鱼，由一种有眼睛的表面居住形式（表面鱼）和一种盲洞穴居住形式（洞穴鱼）组成。眼原基最初在洞穴鱼发育过程中形成，但随后停止和退化，导致失明的成年人。第一个退化的组织是透镜。值得注意的是，将表层鱼胚胎的透镜移植到洞穴鱼的视杯中可以恢复成年洞穴鱼的完整眼睛。我们建议研究透镜调节眼睛生长和发育的分子和细胞基础Astyanax，这是唯一适合于透镜操作。前三个具体的目的是为了确定细胞事件的基础上逮捕的视网膜，角膜和巩膜分化的洞穴鱼类和透镜如何调制这些事件。在这些目标中，我们将联合收割机透镜移植方法与视网膜、角膜和巩膜发育的特异性分子标记物相结合。第四个具体目标是确定候选基因编码晶状体信号因子影响其他眼睛部分的发展。将使用从分离的表面鱼和洞穴鱼晶状体获得的cDNA文库通过消减杂交获得基因。第五个具体目标是确定候选基因在透镜变性和晶状体调节的其他眼组织发育中的作用。这将通过功能丧失和功能获得研究以及利用候选基因的特定特性来完成。我们希望这项研究能够为透镜信号传导过程提供新的见解，并填补我们对正常和异常眼睛发育的理解中的一个主要空白。

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.