Cell Type‐Specific Surface Antigens in the Mammalian Nervous System

Interest in the molecular composition of cell surfaces in the nervous system has emerged from several disciplines in neurobiology. Two lines of investigation in particular have turned to the delineation of the differentiative program of neural cell surfaces: the search for cell surface components involved in cell recognition and interaction during development, and the search for cell surface markers that are unique for a particular cell type and a particular developmental stage. The investigation of cell type-specific markers has been stimulated by the need to understand a cell’s specialized task in performing its particular functional assignments. The advantage in deciphering unique molecular designs on the cell surface rather than intracellular ones lies in the possibility that such constellations may not only be involved in cell recognition, but may also serve as a means for the isolation of homogeneous populations of cell types in viable form. The availability of selected populations of all neural cell classes (encompassing not only the major classes of neurons, astrocytes, and oligodendrocytes, but also developmentally distinct subsets of these) is the basis of much research in cellular and molecular neuro biology. The present review will focus on some major aspects of cell typespecific cell surface markers and will summarize our knowledge of immunologically identified markers in the mammalian nervous system, without allusion to function and with a special emphasis on the mouse cerebellum, which has been the center of interest in the author‘s laboratory. Antibodies have played a crucial role in the characterization of cell type-specific markers. The immunological approach has proven to be an extremely versatile one and its possibilities can be summarized as follows. (1) Antibodies can be used to probe for the function of the antigen by blocking or modifying its task. When directed against different antigenic sites on the molecule, antibodies can serve to locate the structural sites involved in function. (2) When complex mixtures of antigens are used for immunization, new, and sometimes minor, cell surface constituents can be discovered and analyzed with the resultant antibodies. (3) When coupled to visual tags (fluorescein, rhodamine, ferritin, peroxidase, gold, and others), these antibodies can be used to define the cellular and subcellular distribution of the corresponding antigens in cell culture and in histological sections. (4) Antibodies can serve as reagents for the analysis of the molecular nature of the corresponding antigens characterized initially by purely immunological methods. ( 5 ) Cell type-specific antibodies can be used to isolate the antigen-positive and -negative cell types from their mixtures, provided that cells can be obtained as single cell suspensions. Isolation can be achieved by fluorescence-activated cell sorting, which allows cell separation not only within a broad range of fluorescence intensities of cells labeled with fluorochrome-coupled antibody, but also according to cell size and other parameters, such as membrane viscosity (Melamed et al., 1979). The more sophisticated the cell sorter’s sensory and motor machineries, the more parameters can serve for cell isolation in a single sorting process. An alternative, less elegant, but sometimes more rapid method for immunoselection makes use of antibody-coupled solid state carriers, such as Sepharose and polyacrylamide beads and microor macrospheres with magnetic cores (Kronick et al., 1978; Meier et al., 1982). Yet another means of im-