PAX GENE REGULATION IN EMBRYOGENESIS

胚胎发生中的 PAX 基因调控

• 批准号: 2269945
• 负责人: Martyn D Goulding
• 金额: $ 27.58万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2269945
• 关键词: cellular polarity; chick embryo; developmental neurobiology; embryogenesis; genetic disorder; genetic regulation; genetic regulatory element; laboratory mouse; laboratory rabbit; nervous system transplantation; neural plate /tube; spinal cord; transcription factor; vertebrate embryology

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.

在脊椎动物中，神经系统从简单的伪层化发展而来。 上皮，神经外胚层。早期神经外胚层的区域化 导致不同类的位置特定的 神经系统内的神经元。这些基因事件调节着 对细胞命运的位置调控尚不清楚。差动 早期神经系统内的转录活动被认为是 是一个重要的因素。一个配对的盒(Pax)基因家族，编码 转录因子在早期的离散区域表达 神经系统。我们最近分离出了一对盒基因Pax-3，它是 背腹受限早期脊髓的表达 神经前体细胞的群体。我们还分离了这只鸡 Pax-6和Pax-7基因也是背腹受限的 脊髓神经上皮细胞。已知背腹两极起作用 在决定脊髓神经细胞命运中起决定性作用， 使我们相信Pax-3、Pax-6和Pax-7的表达 神经前体是脊髓的重要调节步骤 图案化。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 通过鉴定顺式作用蛋白Pax-3在脊髓中的表达 控制表达的序列和组织。损失的影响 Pax-3功能对神经前体细胞发育的影响 特别是那些引起神经峰的因素也将被检查。 在斑点小鼠身上，目的是定义神经脊中的这些步骤 受Pax-3调控的发育。Pax-3的参与，在 人类遗传性疾病瓦登堡综合征和观察到 在小鼠模型中存在神经管缺陷的数量 瓦登堡综合征，斑点，是一个重要的洞察力的迹象 这些将从这些研究中获得的遗传缺陷。这个 该项目的长期目标是确定Pax-3在神经细胞中的作用 并开始识别调节其表达的信号 脊椎动物神经系统中的模式。