Identifying Genes Involved in Neuronal Differentiation

描述(申请人提供)：哺乳动物的大脑皮层是分层的 结构。我对调节大脑发育的分子很感兴趣 皮质层。 第一个具体目标是识别在形成过程中起关键作用的基因。 特定皮质内神经元的适当轴突投射模式 第5层。第5层神经元最初将轴突分支延伸到许多 皮质下区域。之后，有选择地修剪茂盛的树枝，以便 形成了适当的特定于区域的投影图案。同源域 转录因子Otx1是修剪旺盛的轴突所必需的 树枝。然而，对于河豚毒素L的靶基因以及 轴突修剪机制。我建议找出作用于下游的基因 利用基因芯片技术调控轴突的细化。 第二个目标是分离和研究调节起始层的基因。 命运决定或板层分化的早期阶段。我已经做完了 用原位杂交技术筛选和鉴定了12个新的已知 表现出特定层级表达模式的基因。实验是 建议研究它们在层流命运决定中的潜在作用 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.