DISRUPTION OF HIPPOCAMPAL DEVELOPMENT IN-VIVO BY CR-50 MAB AGAINST REELIN

We previously generated a monoclonal alloantibody, CR-50, by immunizin g reeler mutant mice with homogenates of normal embryonic brains, This antibody recently was shown to recognize a Reelin protein, which is c oded by the recently identified candidate gene for the reeler mutation , However, it is still unclear whether Reelin, especially the CR-50 ep itope region, is indeed responsible for the reeler phenotype in vivo. Here we show that Reelin is localized on Cajal-Retzius neurons in the hippocampus and that intraventricular injection of CR-50 al the embryo nic stage disrupts the organized development of the hippocampus in viv o, converting it to a reeler pattern. Labeling experiments with 5-brom odeoxyuridine demonstrated that the labeled cells in the stratum pyram idale of the CR-50-treated mice mere distributed in a pattern similar to that of reeler. Thus, Cajal-Retzius neurons play a crucial function in hippocampus development, and the CR-50 epitope on Reelin plays a c entral role in this function.