Dispersion Patterns for Retinal Neuroblasts

视网膜的结构复杂性是由一系列控制发育的事件带来的。 增殖、命运决定、迁移、过程生长、目标识别、突触形成和细胞 死亡。这些过程建立了一个精确的分层结构，视网膜神经元位于其中 不同的深度，通过两个中间的突触层连接。叠加在这一层上 组织中，某些单元格类型以有序数组的形式分布在给定层上，以便它们及其 过程，确保在建立与其传入的连接时对视网膜表面进行统一采样 并以神经元为目标。这项研究计划正在寻求了解细胞、分子和遗传 这种图案的决定因素和此类阵列中的连接性，重点关注水平 细胞。对重组近交系水平细胞数量的数量性状分析将首先确定 控制这个神经元群体大小的基因。嵌合小鼠将由亲本菌株产生 水平细胞数量不同，以确定树突场大小是否由细胞固有的VS控制 环境说明。视锥感光细胞的可比数量性状分析也将是 传入者在指定水平细胞的树突图案方面所起的作用将是 在各种基因敲除和重组近交系中检测到，在这些自交系中，球果之间的收敛比率 水平细胞被调节，或者在这些传入和树突之间的神经传递是 被更改或废除的。同型邻居和传入神经在建立神经传导机制中的作用 这种连通性将被确定，检验视觉活动的开始驱动 相邻水平细胞之间的竞争性相互作用，因为它们寻求在 发育中的外丛状层。两个亲本菌株胚胎视网膜的微阵列分析。 显示水平和圆锥体单元格数量的两倍差异将用于识别下游 对建立这些差异至关重要的基因。这些实验将揭示调控 水平细胞和锥体细胞的数量，以及水平细胞建立的生物学机制 在发育过程中，它们的形态模式、树突覆盖以及与锥体传入细胞的连接。

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.