PATTERNING GENES IN RETINAL DEVELOPMENT

描述(改编自申请人的摘要)：长远目标 所提议的研究的目的是确定细胞和分子 导致特定细胞类型分化的发育事件 在脊椎动物的视网膜里。这方面的直接实验方法 目标是重点研究硬骨鱼中HH基因在视网膜发育中的作用 鱼。提出了五个具体目标：(1)表征 HH基因在视网膜色素上皮中的时空表达 (2)实验上降低HH基因在斑马鱼中的表达 斑马鱼胚胎的RPE及其对视网膜细胞的影响 分化和图案化；(3)创建早熟和/或 HH在斑马鱼眼睛中的异位表达及其对 视网膜细胞分化和图案化；(4)检查特定效应 HH蛋白在成人视网膜视杆感受器产生中的作用 金鱼；以及(5)识别接收HH信号的视网膜细胞类型 通过定位HH受体的表达。建议的研究计划 强调HH基因表达在视杆细胞病变过程中的潜在参与 光感受器发育。杆状感光器的丧失是主要事件 在一些遗传性视网膜退行性变中；对可能 参与棒材生产可能最终导致 用于人类的杆状替代疗法的策略。

DESCRIPTION (Adapted from applicant's abstract): The long-range objective of the proposed research is to determine the cellular and molecular developmental events that lead to the differentiation of specific cell types in the vertebrate retina. The immediate experimental approach toward this goal is to focus on the role of hh genes in retinal development in teleost fish. Five specific aims are proposed: (1) to characterize the spatiotemporal expression of hh genes in the retinal pigmented epithelium (RPE) of zebrafish; (2) to experimentally reduce expression of hh genes in the RPE of embryonic zebrafish and examine the effects on retinal cell differentiation and patterning; (3) to create sites of precocious and/or ectopic hh expression in the zebrafish eye and examine the effects on retinal cell differentiation and patterning; (4) to examine specific effects of hh protein on rod photoreceptor production in the retina of adult goldfish; and (5) to identify retinal cell types that receive the hh signal by localizing expression of the hh receptor. The proposed research program emphasizes potential involvement of hh gene expression in the process of rod photoreceptor development. A loss of rod photoreceptors is a primary event in a number of hereditary retinal degenerations; the study of genes that may be involved in rod production may ultimately lead to the development of strategies for rod replacement therapy in humans.