Identifying Genes Involved in Neuronal Differentiation

描述（由申请人提供）：哺乳动物大脑皮层是一个分层的 结构我感兴趣的是调节发育的分子 皮质层 第一个具体的目标是确定基因是关键的形成 特定皮质内神经元的轴突投射模式 层，层5。第5层神经元最初延伸轴突分支到许多 皮质下区域。之后，茂盛的枝条被有选择地修剪， 形成适当的区域特定投影图案。同源结构域 转录因子Otx 1是修剪旺盛的轴突所必需的 树枝然而，关于Otx 1的靶基因或关于Otx 1的靶基因， 轴突修剪的机制。我建议找出在下游起作用的基因 利用基因芯片技术研究Otx 1基因调控轴突细化的作用。 第二个目标是分离和研究调控初始层流的基因， 命运决定或层分化的早期阶段。我已经完成 原位杂交筛选并鉴定了12个新的以及已知的 显示层特异性表达模式的基因。实验 拟研究其在层流归宿决定中的潜在功能 和/或层分化的早期阶段。

DESCRIPTION (provided by applicant): The mammalian cerebral cortex is a layered structure. I am interested in the molecules that regulate development of cortical layers. The first specific aim is to identify genes that are critical in the formation of proper axonal projection patterns for neurons within a specific cortical layer, layer 5. Layer 5 neurons initially extend axonal branches to many subcortical areas. Later the exuberant branches are selectively pruned so that a proper area-specific projection pattern is formed. The homeodomain transcription factor, Otx1, is required for the pruning of exuberant axonal branches. However nothing is known about the target genes of Otx l or about the mechanisms of axonal pruning. I propose to identify genes that act downstream of Otx1 to regulate axonal refinement using cDNA microarray technology. The second aim is to isolate and study genes which regulate the initial laminar fate determination or early stages of laminar differentiation. I have finished an in situ hybridization screening and identified twelve novel as well as known genes that demonstrate layer-specific expression patterns. Experiments are proposed to study their potential functions in laminar fate determination and/or early stages of layer differentiation.