Disruption of hippocampal development in vivo by CR-50 mAb against Reelin

We previously generated a monoclonal alloantibody, CR-50, by immunizing reeler mutant mice with homogenates of normal embryonic brains, This antibody recently was shown to recognize a Reelin protein, which is coded by the recently identified candidate gene for the reeler mutation, However, it is still unclear whether Reelin, especially the CR-50 epitope 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 embryonic stage disrupts the organized development of the hippocampus in vivo, converting it to a reeler pattern. Labeling experiments with 5-bromodeoxyuridine demonstrated that the labeled cells in the stratum pyramidale 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 central role in this function.