CELL INTERACTIONS IN MOTOR NEURON DIFFERENTIATION

发育中脊髓运动神经元分化的研究 提供了一个定义细胞相互作用的模型系统 控制神经细胞识别的诱导因素的分子本质 脊椎动物的神经系统。控制信号的来源和来源 然而，运动神经元亚型的多样化仍不清楚。在……里面 这个项目我们将集中在运动神经元多样性的控制上。 外侧运动柱(LMC)是一类支配运动神经元的神经元 以肢体肌肉为目标。在初步研究中，我们提供了 有证据表明被牵连的三个不同的信号分子 细胞分化和转化中的维甲酸、Ets结构域 Eph家族的转录因子和受体酪氨酸激酶是 由LMC中的运动神经元亚群表达。这些研究表明 对LMC运动神经元亚型多样性的分析可能会提供 关于分子类功能的新信息蕴含了更多 一般在细胞分化和肿瘤发生中起作用。 使用运动神经元分化的体外检测和 大鼠运动神经元基因表达的分子遗传学操作 小鼠胚胎我们将主要解决三个问题：1.类维甲酸的作用 运动神经元柱状亚型同一性规范中的信号传递 在LMC内部。2.ETS转录因子在指定基因表达中的作用 LMC内运动神经元池的同一性。3.伊夫的角色 运动神经元组织中的蛋白酪氨酸激酶及其肾上腺素配体 LMC和运动神经轴突的特定子集向其 四肢中的目标。

The study of motor neuron differentiation in the developing spinal cord has provided a model system for defining the cellular interactions and molecular nature of inducing factors that control neuronal identify in the vertebrate nervous system. The source and origin of signals that control the diversification of motor neuron subtypes however remains unclear. In this project we will focus on the control of motor neuron diversity in the lateral motor column (LMC), a class of motor neurons that innervates target muscles in the limb. In preliminary studies we have provided evidence that three distinct signaling molecules that have been implicated in cellular differentiation and transformation: retinoids, ETS domain transcription factors and receptor tyrosine kinases of the Eph family are expressed by subsets of motor neurons in the LMC. These studies suggest that the analysis of motor neuron subtype diversity in the LMC may provide novel information on the function of classes of molecules implicated more generally in cellular differentiation and oncogenesis. Using a combination of in vitro assays of motor neuron differentiation and molecular genetic manipulations of gene expression in motor neurons in mouse embryo we will address three main issues: 1. The role of retinoid signaling in the specification of motor neuron columnar subtype identity within the LMC. 2. The role of ETS transcription factors in specifying the identity of motor neuron pool identity within the LMC. 3. The role of Eph kinases and their Ephrin ligands in the organization of motor neurons in the LMC and in the projection of specific subsets of motor axons to their targets in the limb.