PAX GENE REGULATION IN EMBRYOGENESIS

在脊椎动物中，神经系统是从一个简单的假复层细胞发展而来的。 上皮，神经外胚层。早期神经外胚层的区域化 导致位置特定的不同类别的 神经系统中的神经元。调节基因的遗传事件 细胞命运的位置调控尚不清楚。微分 早期神经系统内的转录活性被认为 成为一个重要因素。一个家族的配对盒（Pax）基因，编码 转录因子表达在早期的不连续区域， 神经系统我们最近分离出一个配对盒基因，Pax-3， 在脊髓背腹侧限制性损伤的早期表达， 神经祖细胞群。我们还隔离了鸡 Pax-6和Pax-7基因也是背腹限制性的， 脊髓神经上皮众所周知，背腹极性 在决定脊髓中神经元细胞命运中的决定性作用， 这使我们相信，Pax-3、Pax-6和Pax-7的表达可能与细胞凋亡有关。 神经前体是脊髓中重要的调节步骤 模式化这项资助中概述的实验旨在 阐明建立背腹侧的调节相互作用 Pax-3在脊髓中的表达，通过鉴定顺式作用 控制表达的序列和组织。损失的影响 Pax-3对神经前体细胞发育的作用， 特别是那些引起神经嵴的神经也将被检查 在斑点小鼠中，目的是确定神经嵴中的这些步骤， 由圣神-3控制的发展Pax-3参与了 人类遗传性疾病Waardenburg综合征和观察， 许多神经管缺陷存在于以下小鼠模型中： Waardenburg综合征，斑点，是一个重要的见解， 从这些研究中得到的遗传缺陷。的 该项目的长期目标是确定Pax-3在神经系统中的作用。 并开始识别调控其表达的信号 脊椎动物神经系统的模式。

In vertebrates, the nervous system develops from a simple psuedostratified epithelium, the neuroectoderm. Regionalisation of the early neuroectoderm results in the position-specific generation of different classes of neurons within the nervous system. The genetic events that regulate the postional regulation of cell fate are not understood. Differential transcriptional activity within the early nervous system is to believed to be an important factor. A family of paired box (Pax) genes that encode transcription factors are expressed in discrete regions of the early nervous system. We have recently isolated a paired box gene, Pax-3 that is expressed in the early spinal cord in dorso-ventrally restricted populations of neural progenitor cells. We have also isolated the chicken Pax-6 and Pax-7 genes which are also dorso-ventrally restricted in the spinal cord neuroepithelium. It is known that dorso-ventral polarity plays an decisive role in determining neuronal cell fate in the spinal cord, leading us to believe that the expression of Pax-3, Pax-6 and Pax-7 in neural precursors is an important regulatory step in spinal cord patterning. The experiments outlined in this grant are aimed at elucidating the regulatory interactions that establish the dorso-ventral expression of Pax-3 in the spinal cord, by identifying cis-acting sequences and tissues that control expression. The effect that loss of Pax-3 function has on the development of neural precursors cells, in particular those that give rise to the neural crest will also be examined in splotch mice, with the aim of defining those steps in neural crest development that are regulated by Pax-3. The involvement, of Pax-3 in the human hereditary disease Waardenburg Syndrome and the observation that a number of neural tube defects are present in the mouse model of Waardenburg Syndrome, splotch, are an indication of the important insights into these hereditary defects that will be gained from these studies. The long term goal of this project is to define the role of Pax-3 in neural development and begin to identify the signals that regulate its expression pattern in the vertebrate nervous system.