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.

主胸BHLH蛋白是控制神经发展的主要调节剂视网膜和视网膜神经节细胞中棒和锥形感光细胞的分化和无小细胞，以及角膜神经。这些细胞是视力和正确的维护眼睛。主胸BHLH蛋白是仅结合DNA的转录因子具有无处类的e蛋白BHLH蛋白的杂化二聚体，并由ID类拮抗 HLH蛋白。眼睛期间乳牙外功能机制的发育遗传研究开发和差异化将阐明ID蛋白功能的意外新途径已经发现了。要了解这种相互作用蛋白网络的功能，生化方法将用于确定代表性蛋白的各自亲和力彼此，在组织制剂中研究的蛋白质 - 蛋白质相互作用，以验证哪个蛋白质关联发生在体内与活性神经发生的时期相关当神经发育静止时发生。因为各种蛋白质的表达水平是通过蛋白质稳定性调节，并有可能通过调节二聚化亲和力调节调节稳定性和活性的未识别因素将通过遗传筛选寻求用于ID-蛋白外甲虫的修饰符，并使用下一代测序识别方法。预计这些研究将揭示神经发育的新调节因子，这在眼睛。预计这些研究将提出维护和再生健康的新途径组织。