Determination of Retinal Cell Fate

视网膜细胞命运的测定

• 批准号: 7524751
• 负责人: CONSTANCE L CEPKO
• 金额: $ 41.84万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7524751
• 关键词: Affect; Afferent Neurons; Arts; Basic Science; Binding; Binding Sites; Bioinformatics; Blindness; Cells; Color Visions; DNA Sequence; Depth; Development; Engraftment; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genomics; Hereditary Disease; In Vitro; Intervention; Knowledge; Lead; Light Cell; Maps; Mediating; Methods; Nucleic Acids; Photoreceptors; Prevention; Production; Public Health; Published Comment; Regulation; Regulatory Element; Reporter; Retinal; Retinal Cone; Stem cells; Technology; Testing; Therapeutic; Vertebrate Photoreceptors; Vision; cell type; chromatin immunoprecipitation; in vivo; interest; mutant; prevent; retinal rods; transcription factor

DESCRIPTION (provided by applicant): Photoreceptors are the highly specialized sensory neurons that carry out the first step in vision. The mechanisms for the production of photoreceptors during development are of interest from both a basic science and a therapeutic viewpoint. Photoreceptors, particularly rods, the cells that mediate vision in dim light, are the cell type most often directly affected by genetic diseases that lead to blindness. Cone photoreceptors, which mediate our daylight and color vision, also die due to genetic and environmental causes. Replacement of dying photoreceptor cells will require knowledge of the mechanisms of their genesis. For example, stem cells can be instructed to produce rods and/or cones prior to engraftment. In addition, an understanding of photoreceptor development might lead to interventions that prevent developmental abnormalities, which lead to blindness. We propose to investigate the mechanisms by which photoreceptors are generated. The focus will be on the transcription factors that are required for photoreceptor production, including an analysis of their upstream regulators and downstream targets. State-of-the-art nucleic acid technologies that build on our previous genomic studies, as well as our newly developed methods for the study of gene regulation, will be carried out. PUBLIC HEALTH RELEVANCE: Photoreceptors are the highly specialized sensory neurons that carry out the first step in vision. They are often the target of genetic diseases that lead to blindness. We propose to study the mechanisms for the production of photoreceptors, which can lead to the prevention of developmental abnormalities and/or therapies employing engraftment of photoreceptor cells produced by stem cells.

描述（由申请人提供）：光感受器是执行视觉第一步的高度专业的感觉神经元。从基础科学和治疗观点中，在发育过程中生产光感受器的机制引起了人们的关注。感光细胞，尤其是杆，介导视力昏暗的细胞是最直接受到导致失明的遗传疾病的细胞类型。介导我们的日光和色觉的锥形感受器也因遗传和环境原因而死亡。替代垂死的感光细胞将需要了解其起源的机制。例如，可以指示干细胞在植入之前产生棒和/或锥。此外，对感光体发育的理解可能会导致干预措施，从而阻止发育异常，从而导致失明。我们建议研究产生感光体的机制。重点将放在光感受器产生所需的转录因子上，包括对其上游调节器和下游靶标的分析。将基于我们先前的基因组研究以及我们新开发的基因调节研究方法的最先进的核酸技术。公共卫生相关性：光感受器是高度专业的感觉神经元，迈出了远见的第一步。它们通常是导致失明的遗传疾病的目标。我们建议研究产生光感受器的机制，这可能导致采用干​​细胞产生的光感受器细胞的植入的发育异常和/或疗法。