Genetic Control of Topographic Map Formation in the Development of Spinal Circuits

支配哺乳动物至关重要的行为的神经回路，如运动和呼吸，依赖于 运动神经元(MN)与靶细胞建立选择性连接的能力 在外围。支配特定肌肉靶点的运动神经元由 染色体排列的Hox转录因子。HOX基因功能的一个关键方面是分离马达 神经元按地形排列成柱状和池状亚型。虽然有人建议， MNS的躯体定位组织进化为促进日益复杂的肢体的激活 在肌肉学方面，很大程度上还不清楚MN是如何聚集成列的，以及MN位置在塑造中扮演着什么角色 运动网络中连接的专一性。在本提案中，我们将研究PBX的功能 基因--HOX蛋白在MN地形图形成和发育中的重要辅助因子 马达电路。该提案的主要目标是：1)评估PBX基因在组织中的作用 和脊髓运动神经元的连通性，2)确定运动神经元 按地形组织，以及3)确定MN位置和身份在脊柱回路组装中的作用。在……里面 目的1我们将利用遗传操作和组织学方法来确定PBX基因在MN分化中的功能 化验。在AIM2中，我们将确定MNS中PBX蛋白的靶点，并评估它们的功能和机制 监管的影响。在Aim3中，我们将评估运动神经元的位置和身份如何影响 与突触前中间神经元群体的联系。通过建立我们对运动神经元的深入知识 哺乳动物的规范程序，这些研究应该通过以下方式提供对机制的基本见解 组装了哪些马达电路。

The neural circuits governing behaviors vital to mammals, such as locomotion and respiration, rely on the ability of motor neurons (MNs) to establish selective connections with target cells both centrally and peripherally. Motor neurons innervating specific muscle targets are specified by the large family of chromosomally arrayed Hox transcription factors. A key aspect of Hox gene function is to segregate motor neurons into topographically organized columnar and pool subtypes. While it has been suggested the somatotopic organization of MNs evolved to facilitate the activation of an increasingly more complex limb musculature, it is largely unknown how MNs cluster into columns, and what role MN position plays in shaping the specificity of connections within motor networks. In this proposal we will investigate the function of Pbx genes, essential co-factors of Hox proteins, in the formation of MN topographic maps and in the development of motor circuits. The major goals of this proposal are to: 1) to assess the role of Pbx genes in the organization and connectivity of spinal motor neurons, 2) to determine the mechanisms through which motor neurons are topographically organized, and 3) to define the role of MN position and identity in spinal circuit assembly. In Aim1 we will define the function of Pbx genes in MN differentiation using genetic manipulations and histological assays. In Aim2 we will identity the targets of Pbx proteins in MNs, and assess their function and mechanisms of regulation. In Aim3 we will assess how motor neuron position and identity influences the specificity of connections with presynaptic interneuron populations. By building off our in depth knowledge of motor neuron specification programs in mammals, these studies should provide basic insights into the mechanisms through which motor circuits are assembled.