Cell Interaction-Dependent Neural Development

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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.