Hedgehog Signaling in Photoreceptor Differentiation and Maintenance

光感受器分化和维护中的刺猬信号传导

基本信息

批准号：
8389555
负责人：
Xian-Jie Yang
金额：
$ 35.11万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8389555
关键词：
Ablation Adult Affect Animals Apoptosis Attenuated Behavior Bilateral Binding Biological Assay Birth Cell Cycle Progression Cell Maintenance Cell Proliferation Cell Survival Cell physiology Cells Cellular Assay Cellular Structures Defect Development Electron Microscopy Electroretinography Embryo Erinaceidae Event Genes Genetic Recombination Goals Growth Factor Homeostasis Human Integral Membrane Protein Ligands Maintenance Mediating Molecular Molecular Genetics Morphogenesis Morphology Mus Nervous system structure Neural Retina Neurons Outcome Study Pattern Photoreceptors Play Production Proliferating Protein Family Proteins Research Retina Retinal Retinal Cone Retinal Diseases Retinal Ganglion Cells Retinal Photoreceptors Retroviridae Role Signal Pathway Staging Structure Structure of retinal pigment epithelium System Testing Tissues Transgenic Mice Vertebrate Photoreceptors Visual Fields abstracting base combat extracellular genetic analysis human SMO protein insight molecular marker mutant nerve stem cell novel photoreceptor degeneration postnatal progenitor receptor recombinase retinal neuron retinal progenitor cell retinal rods retinogenesis smoothened signaling pathway

Ablation Adult Affect Animals Apoptosis Attenuated Behavior Bilateral Binding Biological Assay Birth Cell Cycle Progression Cell Maintenance Cell Proliferation Cell Survival Cell physiology Cells Cellular Assay Cellular Structures Defect Development Electron Microscopy Electroretinography Embryo Erinaceidae Event Genes Genetic Recombination Goals Growth Factor Homeostasis Human Integral Membrane Protein Ligands Maintenance Mediating Molecular Molecular Genetics Morphogenesis Morphology Mus Nervous system structure Neural Retina Neurons Outcome Study Pattern Photoreceptors Play Production Proliferating Protein Family Proteins Research Retina Retinal Retinal Cone Retinal Diseases Retinal Ganglion Cells Retinal Photoreceptors Retroviridae Role Signal Pathway Staging Structure Structure of retinal pigment epithelium System Testing Tissues Transgenic Mice Vertebrate Photoreceptors Visual Fields abstracting base combat extracellular genetic analysis human SMO protein insight molecular marker mutant nerve stem cell novel photoreceptor degeneration postnatal progenitor receptor recombinase retinal neuron retinal progenitor cell retinal rods retinogenesis smoothened signaling pathway

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项目摘要

Abstract The Hedgehog (Hh) family of proteins plays important roles in the determination of neuronal cell fates and the maintenance of adult neural stem cell potentials. Previous studies and our preliminary results indicate that Sonic hedgehog (Shh) promotes retinal progenitor cell proliferation and affects specification of early born retinal neurons. However, the precise function of Hh signaling in mammalian photoreceptor cell development and survival is not well understood. The proposed research will use molecular genetic approaches to elucidate the roles of Hh signaling during mouse photoreceptor development and maintenance. The essential Hh receptor component Smoothened (Smo) will be eliminated by Cre/loxP recombination using transgenic mouse lines and retroviruses expressing Cre recombinase. The effects of disrupting Hh signaling on postnatal progenitor proliferation and cell fate commitment, and on photoreceptor differentiation and morphogenesis will be analyzed using molecular markers and electron microscopy. The roles of Hh signaling in photoreceptor maintenance and survival will be characterized by ablating the Smo gene or the Shh gene in the mature retina followed by functional and morphological analyses. Results of the proposed research will elucidate the function of an important signaling pathway in mammalian photoreceptor differentiation and survival. Moreover, these studies will provide new insights into mechanisms of photoreceptor degeneration and opportunities to develop novel therapies for combating retinal diseases.

抽象的刺猬（HH）蛋白质家族在确定神经元细胞命运中起着重要作用以及维持成年神经干细胞电位。先前的研究和我们的初步结果表明声音刺猬（SHH）促进视网膜祖细胞增殖并影响早期出生的视网膜神经元的规范。但是，哺乳动物中HH信号的精确功能感光细胞的发育和生存尚不清楚。拟议的研究将使用分子遗传方法阐明HH信号在小鼠感光器中的作用开发和维护。必需的HH受体成分平滑（SMO）是使用表达CRE的转基因小鼠系和逆转录病毒通过CRE/LOXP重组消除重组酶。破坏HH信号对产后祖细胞增殖和细胞命运的影响将使用分子分析承诺，以及对光感受器的分化和形态发生标记和电子显微镜。 HH信号在光感受器维持和生存中的作用将在成熟的视网膜中消除SMO基因或SHH基因的特征功能和形态分析。拟议的研究结果将阐明哺乳动物光感受器分化和存活中的重要信号通路。而且，这些研究将提供有关感光者变性机制的新见解和开发新疗法来打击视网膜疾病的机会。