PATTERNING GENES IN RETINAL DEVELOPMENT

描述（改编自申请人摘要）：长期目标 这项研究的目的是确定 导致特定细胞类型分化的发育事件 在脊椎动物的视网膜上。 直接的实验方法 目的是关注hh基因在硬骨鱼视网膜发育中的作用 鱼. 提出了五个具体目标：（1）表征 视网膜色素上皮中hh基因的时空表达 (RPE)（2）实验性地降低斑马鱼中hh基因的表达， 斑马鱼胚胎视网膜色素上皮细胞的研究 （3）创造早熟和/或 在斑马鱼眼睛中异位hh表达， 视网膜细胞分化和图案化;（4）检查特定的影响 hh蛋白对成年人视网膜视杆细胞产生的影响 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。 拟议的研究计划 强调了hh基因表达在视杆细胞发育过程中的潜在作用 光感受器发育 视杆细胞感光器的丧失是 在一些遗传性视网膜变性;基因的研究， 参与棒生产可能最终导致发展 在人类中的杆替代疗法的策略。

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.