SOX2 is a dose-dependent regulator of retinal neural progenitor competence

SOX2 是视网膜神经祖细胞能力的剂量依赖性调节剂

基本信息

批准号：
7586100
负责人：
Larysa HALYNA Pevny
金额：
$ 36.37万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7586100
关键词：
Ablation Address Affect Alleles Anophthalmos Anterior Area Binding Biological Biological Models Biological Process Cell Differentiation process Cells Cellular Assay Ciliary epithelium Competence Coupled Data Derivation procedure Development Diagnosis Distal Dose Down-Regulation Embryo Epithelial Cells Eye Family member Gene Expression Gene Targeting Generations Genes Genetic Genetic Enhancer Element Genomics Goals Grant HMG Domain HMG-Box Haploidy Hereditary Eye Diseases Human Inherited Iris Knowledge Maintenance Mediator of activation protein Microphthalmos Molecular Morphology Mus Mutant Strains Mice Mutation Nervous system structure Neural Retina Neuraxis Neuroectoderm Neuroectodermal Cell Neuroglia Neuronal Differentiation Neurons Optic vesicle Peripheral Population Positioning Attribute Process Property Protocols documentation Public Health Publishing Reagent Regulation Retina Retinal Role Series Signal Pathway Signal Transduction Staging Stem cell transplant Stem cells Structure Study models Testing Tissues To specify Work base cell type chromatin immunoprecipitation dosage gain of function insight loss of function molecular marker mouse genome mutant nerve stem cell neural plate neurogenesis optic cup postnatal progenitor relating to nervous system retinal progenitor cell retinogenesis tool transcription factor

Ablation Address Affect Alleles Anophthalmos Anterior Area Binding Biological Biological Models Biological Process Cell Differentiation process Cells Cellular Assay Ciliary epithelium Competence Coupled Data Derivation procedure Development Diagnosis Distal Dose Down-Regulation Embryo Epithelial Cells Eye Family member Gene Expression Gene Targeting Generations Genes Genetic Genetic Enhancer Element Genomics Goals Grant HMG Domain HMG-Box Haploidy Hereditary Eye Diseases Human Inherited Iris Knowledge Maintenance Mediator of activation protein Microphthalmos Molecular Morphology Mus Mutant Strains Mice Mutation Nervous system structure Neural Retina Neuraxis Neuroectoderm Neuroectodermal Cell Neuroglia Neuronal Differentiation Neurons Optic vesicle Peripheral Population Positioning Attribute Process Property Protocols documentation Public Health Publishing Reagent Regulation Retina Retinal Role Series Signal Pathway Signal Transduction Staging Stem cell transplant Stem cells Structure Study models Testing Tissues To specify Work base cell type chromatin immunoprecipitation dosage gain of function insight loss of function molecular marker mouse genome mutant nerve stem cell neural plate neurogenesis optic cup postnatal progenitor relating to nervous system retinal progenitor cell retinogenesis tool transcription factor

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项目摘要

DESCRIPTION (provided by applicant): Specification of neural progenitors in the central nervous system (CNS) and maintenance of their proliferative and differentiation capacities largely depend on the function of transcription factors. One such transcription factor, expressed in all neural progenitors of the CNS, is SOX2. We have shown that SOX2 is required for proliferation and differentiation of retinal neural progenitors. Furthermore, we have shown that lowering expression levels of SOX2 (below 40%) in mice results in restriction in retinal progenitor competence and leads to anophthalmia and microphthalmia--conditions observed in 10% of humans with haploid insufficiency in SOX2. Based on these findings we hypothesize that SOX2 functions to specify retinal neural progenitors and to maintain their proliferative and differentiation capacity during the course of retinogenesis. In this study, we will directly assess the effects of Sox2 ablation and reducing its expression levels on the properties of temporally distinct populations of retinal progenitors. PUBLIC HEALTH REVELANCE: We will utilize mouse genetic tools and cellular assays to dissect the molecular mechanisms affected by the expression levels of SOX2 in retinal progenitors.

描述（由申请人提供）：中枢神经系统（CNS）中神经祖细胞的规范及其增殖和分化能力的维持很大程度上取决于转录因子的功能。在中枢神经系统的所有神经祖细胞中表达的一种转录因子是SOX2。我们已经表明，Sox2是视网膜神经祖细胞增殖和分化所必需的。此外，我们已经表明，小鼠的Sox2表达水平（低于40％）会导致视网膜祖细胞能力的限制，并导致疾病和粒细胞感染 - 在Sox2中有单倍体不足的人类中观察到的10％的人数。根据这些发现，我们假设SOX2功能指定视网膜神经祖细胞并在视网膜生成过程中保持其增殖和分化能力。在这项研究中，我们将直接评估SOX2消融的影响，并降低其表达水平对视网膜祖细胞暂时不同种群的性质。公共卫生启示：我们将利用小鼠遗传工具和细胞测定法来剖析视网膜祖细胞中SOX2表达水平影响的分子机制。