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Molecular Genetics of Eye Development

Molecular Genetics of Eye Development
眼睛发育的分子遗传学
批准号:
10318099
负责人:
Nicholas E Baker
金额:
$32.4万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-03-01 至 2023-12-31

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中文摘要
翻译
原神经bHLH蛋白是神经发育的主要调节者,控制着 视网膜视杆细胞和视锥细胞以及视网膜神经节细胞的分化 和无长突细胞,还有角膜神经。这些细胞是视力和正常生活所必需的 眼睛的保养。原神经性bHLH蛋白是仅与DNA结合的转录因子。 与一类普遍存在的E蛋白bHLH蛋白的异源二聚体,并被ID类拮抗 人促黄体生成素蛋白。 眼部大小外毛功能机制的发育遗传学研究 发育和分化将阐明ID-蛋白质功能的意想不到的新途径 它们已经被发现了。为了了解这个相互作用的蛋白质网络的功能, 生物化学方法将被用来确定代表蛋白质各自的亲和力。 以及在组织准备中研究的蛋白质-蛋白质相互作用,以验证 在体内发生的蛋白质关联与活跃的神经发生时期相关,并且 发生在神经发育停滞的时候。因为各种蛋白质的表达水平是 通过蛋白质稳定性调节,并可能通过调节二聚化亲和力, 将通过基因筛查来寻找调节稳定性和活性的未知因素 对于ID蛋白的修饰物,并使用下一代测序进行鉴定 接近。 这些研究有望揭示神经发育的新调节器,这些调节器在 眼睛。这些研究有望提出保持和再生健康眼睛的新途径。 纸巾。
英文摘要
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.
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