Molecular Biology of Retinal Development

视网膜发育的分子生物学

• 批准号: 7363623
• 负责人: SHU-ZHEN WANG
• 金额: $ 31.97万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7363623
• 关键词: Address; Attenuated; Cells; Cellular biology; Clinical; Development; Developmental Biology; Figs - dietary; Funding; Generations; Genes; Genetic; Goals; Homeobox Genes; In Vitro; Knowledge; Label; Learning; Light; Link; Molecular; Molecular Biology; Molecular Biology Techniques; Multipotent Stem Cells; Pathway interactions; Pattern; Photoreceptors; Play; Production; Program Development; Proliferating; Protein Overexpression; Regulation; Replacement Therapy; Repression; Research Personnel; Retina; Retinal; Retinal Photoreceptors; Role; Specific qualifier value; Stem Cell Research; Stem cells; Testing; Therapeutic; Time; Transcriptional Regulation; Ursidae Family; Validation; base; cell type; gain of function; gene function; in vivo; insight; interest; loss of function; neurogenesis; photoreceptor progenitor; progenitor; programs; retinal neuron; retinal progenitor cell

DESCRIPTION (provided by applicant): The long-term goal of this project is to elucidate the molecular regulation of photoreceptor production in the vertebrate retina. This knowledge is imperative to the development of effective stem cell-based photoreceptor replacement therapies. Much needs to be learned about the identities of the genes involved and how they contribute to the selection of the photoreceptor fate from among the other options. Studies during the previous funding period identified neuroD as an instrumental player in photoreceptor differentiation, in a transcriptional pathway of ngn2->neuroD->RaxL. In this pathway, ngn2 functions in multipotent progenitors and its downstream genetic targets include neuroD; neuroD elicits a photoreceptor development program, including the expression of homeobox gene RaxL. In this application we will test the hypothesis that photoreceptor production employs ngn1 at a key step between ngn2 and neuroD. Aim 1 examines whether ngn1 is expressed at the right place and the right time to be a major gene in leading progenitors to the photoreceptor path. Aim 2 investigates whether ngn1 expressly steers progenitors to the photoreceptor path and, thus, leads exclusively to photoreceptor production. Aim 3 determines whether ngn1 is required for photoreceptor production. Aim 4 addresses how ngn1 genetically relates to ngn2 and neuroD during photoreceptor production. These studies will be carried out with a battery of techniques from molecular biology, cell biology, developmental biology, and genetics. This project promises to shed light on the transcriptional regulation governing photoreceptor production. Furthermore, it bears clinical implications. The identification of key genetic players in photoreceptor production will capacitate efficient in vitro or in vivo photoreceptor generation for studies with therapeutic goals. These studies are timely in this era of heightened interest in stem cell research for replacement therapies.

描述（由申请人提供）：该项目的长期目标是阐明脊椎动物视网膜中光感受器产生的分子调节。这种知识对于开发有效的基于干细胞的光感受器替代疗法至关重要。关于所涉及的基因的身份以及它们如何从其他选择中的选择中选择光感受器的命运。在上一个资金期间的研究将Neurod确定为光感受器分化的工具，在NGN2-> Neurod-> raxl的转录途径中。在这一途径中，NGN2在多能祖细胞及其下游遗传靶标中起作用。 Neurod引发了感光器开发程序，包括同型基因raxl的表达。在此应用中，我们将检验以下假设：光感受器的产生在NGN2和NeuroD之间采用NGN1采用NGN1。 AIM 1检查了NGN1是否在正确的位置和正确的时间表达了成为光感受器路径的主要基因。 AIM 2研究NGN1是否明确将祖细胞转向光感受器路径，因此仅导致光感受器的产生。 AIM 3确定是否需要Ngn1才能产生光感受器。 AIM 4解决了光感受器产生期间NGN1与NGN2和NeuroD的遗传关系。这些研究将通过分子生物学，细胞生物学，发育生物学和遗传学的一系列技术进行。该项目有望阐明控制光感受器生产的转录调节。此外，它具有临床意义。在光感受器产生中鉴定关键的遗传参与者将使体外或体内光感受器的产生有效地进行治疗目标研究。在这个对替代疗法的干细胞研究兴趣越来越高的时代，这些研究是及时的。