Development of Retinal Bipolar Cells

摘要 脊椎动物视网膜的细胞结构和连通性非常保守 跨物种。这些视网膜的最大区别是每个视网膜的相对数量 不同的细胞类型。即使在一个物种内，神经元的大小也有显著的差异。 人口。控制调控细胞生产、命运的过程的多态基因 分配和生存是造成个人和现在之间这种差异的主要原因 调查将寻求确定导致这种变异的基因，并了解它们的 在调控增殖、决定命运和细胞凋亡的过程中发挥作用。二十六岁 由A/J和C57BL/6J品系衍生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，以及 将检查不同细胞类型之间的协变程度。双极细胞数量的变化 也将与视锥感光细胞数量的数据进行比较，并与 杆状感光器。细胞数量的变异将被映射到候选的基因组座位 将使用基因敲除策略识别和测试多态基因。细胞的作用 将评估在确定双极细胞数量时的死亡及其时间发生情况。 直接在BAX基因敲除小鼠中，而它的传入依赖将被定义为无锥和 圆锥体突变小鼠。其他类型的细胞已经被证明具有它们的形态 分化由相邻类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制以确定它们对 双极细胞树突的分化。最后，对该基因进行了发育转录组分析 视网膜将在这些重组近交系的每一个中进行，并提供 给NerveNetwork上的科学界。这将允许直接映射 基因表达与基因组位置的差异，从而有助于确定候选基因 导致上述双极细胞和感光细胞数量变化的基因，以及 检测基因表达的相关性以确定参与基因表达的调控网络 生产各种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，澄清我们对视网膜的理解 发展，以及识别可能导致视网膜疾病的基因多态。

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.