Development of Retinal Bipolar Cells

视网膜双极细胞的发育

• 批准号: 8594252
• 负责人: BENJAMIN E REESE
• 金额: $ 34.8万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8594252
• 关键词: Apoptosis; Architecture; Breeding; Candidate Disease Gene; Cell Count; Cell Death; Cell Density; Cell Survival; Cells; Cellular Morphology; Communities; Data; Databases; Dendrites; Dependency; Detection; Development; Developmental Gene; Event; Exhibits; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genomics; Haplotypes; Harvest; Inbred Strains Mice; Individual; Inherited; Inner Nuclear Layer; Investigation; Knock-out; Knockout Mice; Label; Laboratories; LoxP-flanked allele; Maps; Messenger RNA; Microarray Analysis; Molecular Genetics; Morphogenesis; Morphology; Mouse Strains; Mus; Mutant Strains Mice; Neurons; Output; Pattern; Photoreceptors; Play; Population; Predisposition; Process; Production; Quantitative Trait Loci; Recombinant Inbred Strain; Relative (related person); Replacement Therapy; Research; Research Proposals; Resources; Retina; Retinal; Retinal Cone; Retinal Diseases; Role; Signal Transduction; Source; System; Testing; Transcript; Variant; cell type; consomic; density; gene function; horizontal cell; nerve supply; outer plexiform layer; programs; relating to nervous system; research study; retinal rods

ABSTRACT The cellular architecture and connectivity of the vertebrate retina is remarkably conserved across species. What distinguishes these retinas most is the relative numbers of each of the different cell types. Even within a species, there is significant variation in the size of neuronal populations. Polymorphic genes controlling the processes regulating cellular production, fate assignment and survival contribute most of this variation between individuals, and the present investigation will seek to identify genes responsible for this variation, and to understand their role in those processes modulating proliferation, fate determination and apoptosis. Twenty-six recombinant inbred strains of mice derived from the A/J and C57BL/6J strains of mice will be used to determine the natural variation in four different types of retinal bipolar cell, and the degree of co-variation between cell types will be examined. The variation in bipolar cell number will also be compared with data for cone photoreceptor number and with new data collected for rod photoreceptors. Variation in cell number will be mapped to genomic loci where candidate polymorphic genes will be identified and tested using gene knock-out strategies. The role of cell death in establishing bipolar cell numbers, and its temporal occurrence, will be assessed directly in Bax knock-out mice, while its afferent-dependency will be defined in coneless and conefull mutant mice. Other cell types have been shown to have their morphological differentiation controlled by the density of neighboring like-type cells as well as by their afferents, and so each of these variables will be modulated to determine their effects upon the differentiation of bipolar cell dendrites. Finally, a developmental transcriptome analysis of the retina will be conducted in these each of these recombinant inbred strains, and made available to the scientific community on-line at NerveNetwork. This will enable the direct mapping of variations in gene expression to genomic loci, thereby aiding in the identification of candidate genes underlying the above variations in bipolar and photoreceptor cell number, and the detection of correlations in gene expression to identify regulatory networks that participate in the production of individual types of bipolar or photoreceptor cells. These experiments will reveal the determinants of nerve cell number and morphology, clarifying our understanding of retinal development, as well as identifying gene polymorphisms that may contribute to retinal disease.

摘要 脊椎动物视网膜的细胞结构和连通性是非常保守的 跨越物种。最能区分这些视网膜的是每种视网膜的相对数量。 不同的细胞类型即使在同一个物种中，神经元的大小也有很大的差异。 人口。控制调节细胞生产、命运的过程的多态基因 分配和生存贡献了个体之间的大部分差异，而现在， 研究将试图确定负责这种变异的基因，并了解它们的功能。 在调节增殖、命运决定和凋亡的过程中起作用。二十六 来自A/J和C57 BL/6 J小鼠品系的重组近交系小鼠将被 用于确定四种不同类型的视网膜双极细胞的自然变异， 将检查细胞类型之间的共变程度。双极细胞数量的变化 还将与锥光感受器数量的数据和收集的新数据进行比较， 杆状光感受器细胞数量的变化将被映射到基因组基因座，其中候选细胞将被定位到基因组基因座。 将使用基因敲除策略鉴定和测试多态性基因。细胞的作用 将评估确定双极细胞数量时的死亡及其时间发生率 直接在Bax基因敲除小鼠中，而其传入依赖性将在无锥细胞和 锥形突变小鼠。其他细胞类型已被证明具有其形态学特征。 分化由邻近的相似型细胞的密度以及它们的 因此，这些变量中的每一个都将被调节，以确定它们对神经元的影响。 双极细胞树突的分化。最后，我们用发育转录组分析了 视网膜将进行这些每一个这些重组近交系，并提供 在NerveNetwork上的科学社区。这将使直接映射 基因表达的变异与基因组基因座，从而有助于鉴定候选 在双极细胞和感光细胞数量上的上述变化背后的基因，以及 检测基因表达中的相关性，以鉴定参与基因表达的调控网络。 产生个别类型的双极细胞或感光细胞。这些实验将揭示 神经细胞数量和形态的决定因素，澄清了我们对视网膜病变的理解。 发展，以及识别可能导致视网膜疾病的基因多态性。