EARLY EVENTS IN CORTICAL DEVELOPMENT

长期目标是定义和描述发展 引导正确的解剖和功能机制 哺乳动物新皮层的组织及其连接。 的 新皮层处理视觉听觉和躯体感觉， 感知、意志运动反应以及更复杂的现象 比如学习和记忆。 这些职能由 新皮层的功能专门化区域，每个区域的特征在于： 独特的连接性和架构。 丘脑皮层输入发挥a 定义新皮质区的基本作用：在成人中， 决定了一个区域的功能特性。 期间 在发育过程中，丘脑皮质传入神经是正确的 新皮质区的分化。 大脑皮层和大脑皮层 功能和发展是定义控制机制， 从背侧丘脑到新皮质的丘脑皮质轴突的路径发现， 以及随后这些轴突的区域特异性靶向， 适当的皮层区域。 前三个目标针对这些问题 通过测试参与的机制和分子的假设， 丘脑皮层轴突的寻路和区域特异性靶向。 我们 目的是确定吸引和排斥轴突导向的作用 分子，包括化学引诱剂Netrin-1和化学排斥剂 Sema III/D在丘脑皮质轴突寻路中的作用，以及 调控基因EMx 1、EMx 2和Pax 6在控制 特定区域丘脑皮质投射的发展。 第四 目的是解决假设的作用，Emx 1，Emx 2，和Pax 6在 蛋鸡皮层输出神经元区域特性的遗传调控 6和5，侧重于对2005 - 2007年具体目标的具体地区预测， 背侧丘脑，或中脑、后脑和脊髓， 分别 为了实现这些目标，我们将使用 方法，包括体内和体外实验，以表征 轴突导向活性，使用基因敲除小鼠的功能丧失分析 缺乏假设参与的基因， 研究使用重组腺病毒表达这些基因， 胚胎前脑 由于保守的结构和功能 啮齿动物和人类之间的基因同源性，确定的机制 在啮齿类动物模型中，预期与人类相似 发展

The long term objective is to define and characterize the developmental mechanisms which direct the correct anatomical and functional organization of the mammalian neocortex and its connections. The neocortex processes visual, auditory and somatic sensation giving rise to perception, volitional motor responses, and to more complex phenomena such as learning and memory. These functions are performed by the functionally specialized areas of the neocortex, each characterized by unique connectivity and architecture. Thalamocortical input play a fundamental role in defining neocortical areas: in adult, the modality of thalamic input dictates an area's functional identity. During development, thalmocortical afferents are required for the proper differentiation of neocortical areas. A crucial issue in both cortical function and development is defining the mechanisms that control the pathfinding of thalamocortical axons from dorsal thalamus to neocortex, and the subsequent area-specific targeting of these axons to their appropriate cortical areas. The first three aims address these issues by testing hypotheses on mechanisms and molecules involved in the pathfinding and area-specific targeting of thalamocortical axons. Our goal is to define roles of attractant and repellant axon guidance molecules, including the chemoattractant Netrin-1 and the chemorepellant Sema III/D, in pathfinding of thalamocortical axons, and the roles of the regulatory genes EMx1, Emx2, and Pax6 in controlling the development of area-specific thalamocortical projections. The fourth aim addresses hypotheses on the roles of Emx1, Emx2, and Pax6 in the genetic regulation of area identity of cortical output neurons in layers 6 and 5, focusing on their area-specific projections to targets in dorsal thalmus, or in the midbrain, hindbrain, and spinal cord, respectively. To accomplish these aims we will use complementary approaches, including in vivo and in vitro experiments to characterize axon guidance activities, loss of function analyses using knockout mice deficient for genes hypothesized to be involved, and gain of function studies using recombinant adenoviruses to express these genes in embryonic forebrain. Due to the conserved structural and functional homology of genes between rodents and humans, the mechanisms identified in the rodent model are anticipated to be similarly involved in human development.