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Molecular Genetics of Eye Development

眼睛发育的分子遗传学

基本信息

批准号：
10318099
负责人：
Nicholas E Baker
金额：
$ 32.4万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10318099
关键词：
Affect Affinity Amacrine Cells BHLH Protein Binding Binding Proteins Biochemical Biological Assay Blindness Caspase Cells Complex Cornea DNA DNA Binding Development Developmental Process Dimerization Disease Drosophila eye Drosophila genus Eye Eye Development Gene Expression Gene Proteins Genes Genetic Genetic Screening Genetic Transcription Genetic study Health Heterodimerization In Vitro Inhibitor of Differentiation Proteins Ligation Macular degeneration Maintenance Mammals Methods Modeling Molecular Molecular Genetics Mosaicism Natural regeneration Nerve Neurons Pathway interactions Pattern Photoreceptors Point Mutation Post-Translational Regulation Proteins Regulation Retina Retinal Cone Retinal Ganglion Cells Role Route Signal Transduction Specificity Tissues Tumor Suppressor Proteins Usher Syndrome Vision Visual system structure developmental genetics experimental study ganglion cell genomic locus horizontal cell human disease in vivo insight mutant nerve supply neurodevelopment neurogenesis neuroregulation next generation sequencing null mutation preference prevent protein expression protein function protein protein interaction restraint retinal rods stem cells tissue preparation transcription factor visual processing

项目摘要

Proneural bHLH proteins are master regulators of neural development that control the differentiation of rod and cone photoreceptor cells in the retina as well as retinal ganglion cells and amacrine cells, and also corneal nerves. These cells are required for vision and proper maintenance of the eye. Proneural bHLH proteins are transcription factors that only bind DNA in heterodimers with a ubiquitous class of E-protein bHLH proteins and are antagonized by the ID-class of HLH proteins. Developmental genetic studies of the mechanisms of Extramacrochaetae function during eye development and differentiation will elucidate the unexpected new pathways of ID-protein function that have been discovered. To understand the function of this network of interacting proteins, biochemical methods will be used to determine the respective affinities of representative proteins for one another, and protein-protein interactions studied in tissue preparations to verify which protein associations occur in vivo in correlation with periods of active neurogenesis and which occur when neural development is quiescent. Because expression levels of the various proteins are regulated through protein stability, and potentially through modulation of dimerization affinities, the unidentified factors regulating stability and activity will be sought through genetic screens for modifiers of the ID-protein Extramacrochaetae and identified using a next-generation sequencing approach. These studies are expected to reveal new regulators of neural development that are important in the eye. These studies are expected to suggest new routes to maintain and regenerate healthy eye tissues.

前神经bHLH蛋白是神经发育的主要调节因子，视网膜中视杆和视锥感光细胞以及视网膜神经节细胞的分化无长突细胞和角膜神经。这些细胞是视力和正常视力所必需的。眼睛的保养。前神经bHLH蛋白是仅结合DNA的转录因子，异二聚体与普遍存在的一类E-蛋白bHLH蛋白，并拮抗ID类 HLH蛋白质。外毛纲动物眼功能的发育遗传学研究发育和分化将阐明ID蛋白功能的意外新途径已经被发现了。为了了解这种相互作用蛋白质网络的功能，将使用生物化学方法来确定代表性蛋白质的各自亲和力在组织制备中研究蛋白质-蛋白质相互作用，以验证蛋白质结合在体内与活跃的神经发生期相关，发生在神经发育处于静止状态时。因为各种蛋白质的表达水平通过蛋白质稳定性调节，并可能通过调节二聚化亲和力，将通过遗传筛选来寻找调节稳定性和活性的未鉴定的因子 ID-蛋白Extramacrochaetae的修饰剂，并使用下一代测序进行鉴定 approach. 这些研究有望揭示神经发育的新调节因子，这些调节因子在神经发育中非常重要。眼睛这些研究有望为维持和再生健康眼睛提供新的途径组织中