The major long range goal of this work is to understand the mechanisms that control the expression of important neuronal properties during the development of the mammalian central nervous system. We plan to use monoclonal antibodies (MAbs) which recognize subsets of neurons to determine when cell specific antigens are first expressed. In particular, we wish to find out if cell specific antigen expression occurs in dividing stem cells that are the progenitors of the mature neuron or if the final mitosis must occur before cell specific antigen expression begins. We would also like to find out if the formation of appropriate connections is necessary in order to either initiate or maintain expression of cell specific antigens. One part of the proposal is to investigate these questions using two newly discovered MAbs. RB-8 stains a subset of rat olfactory sensory cells and their axons. We will study the distribution of RB-8 staining in the embryonic and adult olfactory bulb. In the adult we will map the distribution of RB-8 positive fibers over the entire extent of the bulb. We will do this in several adult rats to see if this pattern is invariant or if it varies from animal to animal. The development of RB-8 staining will be carefully followed in embryonic and young animals. Finally, the pattern of RB-8 staining in regenerating olfactory projections will be determined. RB-6 was seleted because, in the retina, it stains only the retinal ganglion cells. In the case of RB-6 we will observe the appearance of antigen positive cells in retinas before, during and after the birth of ganglion cells. The expression of RB-6 antigen in vitro will also be studied to determine if the presence of target cells influences antigen expression. Monoclonal antibodies which recognize cell surface antigens on subsets of neurons will prove important in future research in this area. Part of our efforts will be directed towards selecting new monoclonal antibodies with these attributes. We will use both neural tumors and membranes from the developing brain to immunize mice and produce additional hybridomas. All work will be carried out using rat cells and membranes as the rat now appears to be the most intensively studied vertebrate as far as CNS biology is concerned.
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