Cell Interaction-Dependent Neural Development

细胞相互作用依赖的神经发育[Paul J. linserabstract]像神经系统这样的复杂组织是由许多不同类型的细胞组成的，这些细胞共同作用产生组织的净输出。神经系统中细胞的两个主要子类是神经元和神经胶质细胞。这些是高度特化的细胞类型，它们执行互补但截然不同的任务。这些不同类型的细胞是如何在胚胎发育过程中产生的，这是Paul J. Linser教授实验室研究的中心焦点。在对影响胚胎细胞选择成为神经元细胞或神经胶质细胞的机制进行了20多年的研究过程中，Linser博士的团队发现了一种细胞表面糖蛋白，它似乎参与了这一发育决定。这种蛋白质被称为5A11/basigin，存在于几种组织中，但在神经视网膜和大脑中表达非常高。已经培育出一种5A11/basigin基因失活的小鼠。这些小鼠为研究这种蛋白质的实际功能提供了一个绝佳的机会。5A11/basigin基因敲除小鼠表现出的异常之一是失明。虽然这些小鼠的视网膜神经最初看起来发育正常，但它们从未真正发挥接收和解释图像（光）信号的功能。Linser博士的研究重点是利用基因敲除小鼠来帮助理解5A11/basigin在正常和功能的神经视网膜发育中所起的特定作用。该研究将结合分子生物学和生物化学技术，详细研究在缺乏5A11/盆地蛋白的情况下发生的发育变化。由于这种蛋白在许多组织中表达，敲除小鼠还表现出许多其他特征，这些特征大大降低了它们的生物稳定性。了解5A11/basigin糖蛋白在神经视网膜中的功能，将有助于了解这种蛋白和其他具有类似结构的蛋白如何在正常动物发育中发挥作用。

Cell Interaction-dependent Neural DevelopmentPI: Paul J. LinserAbstractComplex tissues such as the nervous system are composed of numerous distinct types of cells that work together to produce the net output of that tissue. Two major sub-categories of cells in the nervous system are neurons and neuroglia. These are highly specialized cell types that perform complementary but distinctly different tasks. How it is that these disparate cell types arise during embryonic development is a central focus of the research in the laboratory of Professor Paul J. Linser. During the course of over 20 years of research into the mechanisms that influence an embryonic cell's choice to become either a neuron or a neurglial cell, Dr. Linser's group discovered a cell surface glycoprotein that seems to participate in this developmental decision. The protein is called 5A11/basigin and is found in several tissues but is very highly expressed in neural retina and brain. A line of mice has been produced in which the gene for 5A11/basigin has been inactivated. These mice afford a remarkable opportunity for studying the actual function of this protein. Among the abnormalities exhibited by the 5A11/basigin knockout mice is blindness. Although the neural retinas of these mice initially appear to develop normally, they never actually become functional as receivers and interpreters of image (light) signals. The focus of Dr. Linser's research is on the use of the knockout mouse to help understand the specific role that 5A11/basigin plays in the development of a normal and functioning neural retina. The proposed studies will combine techniques of molecular biology and biochemistry to examine in great detail the developmental changes that have arisen in the absence of the 5A11/basigin protein. As this protein is expressed in numerous tissues, the knockout mice also exhibit a number of other characteristics that greatly diminish their biological stability. Understanding the function of the 5A11/basigin glycoprotein in the neural retina will lead to fundamental insights into how this protein and others with similar structure serve in normal animal development.