CELL INTERACTIONS IN MOTOR NEURON DIFFERENTIATION

发育中脊髓运动神经元分化的研究 提供了一个模型系统，用于定义细胞相互作用， 诱导因子的分子性质控制神经元的鉴定， 脊椎动物的神经系统信号的来源和起源， 然而，运动神经元亚型的多样化仍然不清楚。在 这个项目，我们将集中在运动神经元多样性的控制， 外侧运动柱（LMC），一类支配 瞄准肢体的肌肉在初步研究中，我们提供了 有证据表明三种不同的信号分子 在细胞分化和转化中：类维生素A，ETS结构域 Eph家族的转录因子和受体酪氨酸激酶是 由LMC中运动神经元的子集表达。这些研究表明 LMC中运动神经元亚型多样性的分析可以提供 新的信息的功能类分子牵连更多 通常在细胞分化和肿瘤发生中。 使用运动神经元分化的体外测定和 运动神经元基因表达的分子遗传学操作 小鼠胚胎，我们将解决三个主要问题：1。类维生素A的作用 运动神经元柱状亚型身份特化中的信号传导 在LMC。2. ETS转录因子在指定转录因子中的作用 LMC内运动神经元池的同一性。3. Eph的作用 激酶及其肝配蛋白配体在运动神经元组织中的作用 LMC和特定运动轴突亚群向其投射中， 肢体中的目标

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.