ABSTRACT 9723874 LINSER The central nervous system (CNS) is composed of two major and distinct populations of cells: neurons and neuroglia. In many ways, neurons and neuroglia are specialized to perform distinct although complementary tasks. Indeed, it is currently believed that the "functional unit" of the nervous system is a neuron and its obligatory associated neuroglia. Although the neurons and neuroglia of the mature CNS are functionally and structurally distinct, both cell types come from common progenitor cells during neural development. The cellular and molecular mechanisms that control cell differentiation during embryogenesis are the focus this research. Specifically, Dr. Linser's laboratory has identified a unique cell-surface glycoprotein that is involved in the final decision of progenitor cells in the retina of the eye to differentiate as neuroglial cells. In the current project, they will investigate how this cell-surface protein, called the 5A11 antigen, influences glial cell phenotype maturation. The analyses will include the use of engineered retroviral vectors to introduce genetic markers as well as to bring about changes in expression of the 5A11 gene. As neuronal and glial cell differentiation seems to be tied to when a cell stops dividing, the project has an overriding focus on the events of cell differentiation relative to "terminal" or the last cell division. In addition, this study will compare and contrast the role of the 5A11 antigen with that of two, well characterized cell-cell recognition molecules, integrin and N-cadherin. The technical approaches to be used rely heavily on current state-of-the-art molecular biology, biochemistry, tissue culture and immunohistochemistry. The proposed studies are designed to shed light on the fundamental cell-cell recognition processes that provide the driving force for neuroglial cell differentiation. Since neurons and neuroglia are so different from one another and yet share a common cell of origin, underst anding the mechanisms that give rise to these different cell types will also provide insight into the fundamental processes of cell differentiation.
