Dispersion Patterns for Retinal Neuroblasts

视网膜结构的复杂性是由一系列发育事件引起的， 增殖、命运决定、迁移、过程生长、靶识别、突触发生和细胞 死亡这些过程建立了一个精确的分层结构，其中视网膜神经元位于 不同的深度，通过两个中间的突触层连接。叠加在这个分层的 组织，某些细胞类型作为有序阵列分布在给定层上，使得它们及其 过程，确保视网膜表面的均匀采样，因为它们与它们的传入神经建立连接。 和靶神经元。这项研究计划旨在了解细胞，分子和遗传 这种模式和连接在这样的阵列的决定因素，集中在人口水平 细胞重组近交系中水平细胞数的数量性状分析将首先鉴定 控制神经元数量的基因。嵌合小鼠将由亲本品系产生 不同的水平细胞数量，以确定树突状领域的大小是否是由细胞内在与 环境指示。一个可比较的数量性状分析的锥光感受器也将是 进行，传入神经在指定水平细胞的树突图案中所起的作用将被 在各种敲除和重组近交系中进行了检查， 和水平细胞被调制，或者在这些传入神经和树突之间的神经传递被调制， 改变或废除。同型邻居和传入神经在神经元的建立中所起的作用 这种连通性将被确定，检查假设，即视觉活动的开始驱动一个 相邻水平细胞之间的竞争性相互作用，因为它们试图殖民个别蒂， 正在发育的外丛状层。两个亲本品系胚胎视网膜的微阵列分析。 显示水平和锥细胞数量的两倍差异将用于识别下游 这些基因对这些差异的形成至关重要。这些实验将揭示调控基因 水平和锥细胞的数量，以及水平细胞建立的生物学机制 它们的形态模式、树突覆盖和发育过程中与视锥传入神经的连接。

The architectural complexity of the retina is brought about by a series of developmental events controlling" proliferation, fate determination, migration, process outgrowth, target recognition, synaptogenesis and cell death. These processes establish a precisely layered structure in which retinal neurons become positioned at different depths, connected via two intervening synaptic layers. Superimposed upon this layered organization, certain cell types are distributed as orderly arrays across a given layer so that they, and their processes, ensure a uniform sampling of the retinal surface as they establish connectivity with their afferent and target neurons. This research program is seeking to understand the cellular, molecular and genetic determinants of this patterning and connectivity in such arrays, focusing upon the population of horizontal cells. A quantitative trait analysis of horizontal cell number in recombinant inbred strains will first identify genes that control the size of this neuronal population. Chimeric mice will be produced from parental strains that differ in horizontal cell number, to determine whether dendritic field size is controlled by cell-intrinsic vs environmental instructions. A comparable quantitative trait analysis of the cone photoreceptors will also be conducted, and the role played by the afferents in specifying dendritic patterning of horizontal cells will be examined in various knockout and recombinant inbred strains in which the convergence ratio between cones and horizontal cells is modulated, or in which neurotransmissionbetween these afferents and the dendrites is altered or abolished. The roles played by both homotypic neighbors and by afferents in the establishment of this connectivity will be determined, examining the hypothesis that the onset of visual activity drives a competitive interaction between neighboring horizontal cells as they seek to colonize individual pedicles in the developing outer plexiform layer. Microarray analysis of embryonicretina from .two parental strains . showing a two-fold difference in both horizontal and cone cell number will be used to identify downstream genes critical for the establishment of these differences. These experiments will reveal the genes that regulate horizontal and cone cell number, as well as the biological mechanisms by which horizontal cells establish their morphological patterning, dendritic coverage and connectivity with cone afferents during development.