The Role of the Nkx 6.1 and Homeobox Genes in the Control of Motoneuron and Oligodendrocyte Development

[9808126]发育神经科学的基本目标之一是确定神经系统中大量不同类型的细胞如何从胚胎神经上皮中分化出来。邱梦生博士的实验室正在研究在动物发育的早期阶段，引导发育中的神经系统中的幼稚细胞变成运动神经元和少突胶质细胞（一种胶质细胞）的分子事件。最近，邱博士发现了两个新的转录因子，命名为Nkx-6.1和Nkx-6.2，它们是在胚胎脊髓腹侧运动神经元和少突胶质细胞的神经上皮祖细胞中特异性合成的。邱博士的团队将使用两种遗传方法研究这两个基因在控制运动神经元和少突胶质细胞的规范和分化中的功能作用。首先，他们将分别或联合从小鼠基因组中删除Nkx-6.1和Nkx-6.2基因，并研究运动神经元和少突胶质细胞的发育如何受到影响。这一系列的研究将提供关于Nkx-6.1和Nkx-6.2产品对运动神经元和少突胶质细胞的正常发育是否必要的信息。其次，他们将生产另一种转基因小鼠系，在这种小鼠系中，Nkx-6.1基因的表达可以在脊髓背部未分化的神经细胞中被特异性诱导。然后，他们将检查是否有额外的运动神经元或少突胶质细胞由脊髓背细胞产生，这些细胞通常不会成为运动神经元。这项研究将告诉我们Nkx-6.1或Nkx-6.2基因表达是否能够启动未分化神经上皮细胞中整个运动神经元和/或少突胶质细胞的发育程序。

9808126 QIU One of the fundamental goals of developmental neuroscience is to determine how the large variety of distinct cell types in the nervous system become differentiated out of the embryonic neuroepithelium. Dr. Mengsheng Qiu's laboratory is studying the molecular events that instruct naive cells in the developing nervous system to become motor neurons and oligodendrocytes (a type of glial cell) at an early stage of animal development. Recently, Dr. Qiu has identified two novel transcription factors, named Nkx-6.1 and Nkx-6.2, that are specifically synthesized in the neuroepithelial progenitor cells of motor neurons and oligodendrocytes in the ventral part of the embryonic spinal cord. Dr. Qiu's group will study the functional role of these two genes in the control of motor neuron and oligodendrocyte specification and differentiation using two genetic approaches. First, they will delete the Nkx-6.1 and Nkx-6.2 genes from the mouse genome, both separately and in combination, and investigate how the development of motor neurons and oligodendrocytes is affected. This line of research will provide information on whether the Nkx-6.1 and Nkx-6.2 products are necessary for the normal development of motor neurons and oligodendrocytes. Second, they will produce another genetically-altered mouse line in which Nkx-6.1 gene expression can be specifically induced in the undifferentiated neural cells of the dorsal portion of spinal cord. They will then examine if additional motor neurons or oligodendrocytes are produced by dorsal spinal cord cells, which normally do not become motor neurons. This study will inform us whether Nkx-6.1 or Nkx-6.2 gene expression is capable of initiating the entire motor neuron and/or oligodendrocyte developmental program in undifferentiated neuroepithelial cells.