The role of Pax6 gene in vertebrate neural development

在大脑的发育过程中，产生了许多不同类型的神经元，并将其传递到正确的位置，轴突投射自己的目标，以形成正确的神经元网络。发育神经生物学的最新进展表明，这种神经元的定位和轴突投射是基于大脑的模式。Pax 6是脊椎动物Pax基因家族的成员，编码转录因子。Pax 6在发育中的前脑、后脑和脊髓中的离散域中表达。该研究项目旨在阐明Pax 6在细胞和分子水平上对大脑模式化的作用。在本基金资助期间，我们获得了以下结果：1）在小鼠全胚胎培养条件下，我们对Dil标记的神经上皮细胞进行了示踪，并在细胞水平上阐明了皮质和纹状体之间的边界是何时以及如何形成的。2）原位杂交揭示了钙粘蛋白细胞粘附分子Rcadherin和cadherin 6的两个成员的独特表达模式，在皮层和纹状体，3）将外源基因电穿孔到培养的小鼠胚胎中表明，这些钙粘蛋白的排他性表达模式在维持皮质/纹状体边界中起重要作用。追踪cadherin 6基因敲除小鼠的神经上皮细胞发现，皮质和纹状体之间的边界形成，但纹状体神经上皮细胞的运动增加

During development of the brain, numerous neurons of various different types are generated and delivered at their right positions, and the axons project their own targets to make correct neuronal networks. Recent advance in developmental neurobiology has revealed that such neuronal localization and axonal projection are based on the brain patterning. Pax6 is a member of the vertebrate Pax gene family, which encode transcriptional factors. Pax6 is expressed in discrete domains in the developing forebrain, hindbrain, and spinal cord. This research project aimed to elucidate roles of Pax6 in patterning the brain at cellular and molecular levels. We obtained the following results during the period supported by this grant.1) We performed tracing of neuroepithelial cells labeled with Dil under mouse whole embryo culture, and elucidated when and how the boundary between the cortex and striatum is formed at the cellular level.2) In situ hybridization revealed exclusive expression patterns of the two members of cadherin cell adhesion molecules, Rcadherin and cadherin6, in the cortex and striatum, respectively.3) Electroporation of exogenous genes into the cultured mouse embryos demonstrated that exclusive expression patterns these cadherins play important roles in maintaining the cortex/striatum boundary.4) Tracing neuroepithelial cells in the cadherin6 knockout mice revealed that the boundary between the cortex and striatum was formed but that movement of the striatal neuroepithelial cells increased.