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

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

^*Molecular Neurobiology Laboratory, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Tsukuba, Ibaraki 305, Japan; ^‡Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108, Japan; and ^§Department of Physiology, Kochi Medical School, Nankoku, Kochi 783, Japan

Abstract

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 at 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 were 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.

Footnotes

↵ † To whom reprint requests should be sent at: Molecular Neurobiology Laboratory, The Institute of Physical and Chemical Research (RIKEN), 3–1-1 Koyadai, Tsukuba, Ibaraki 305, Japan. e-mail address: nakajima{at}rtc.riken.go.jp.
Thomas S. Reese, National Institutes of Health, Bethesda, MD
ABBREVIATIONS:

BrdUrd,

5-bromodeoxyuridine;

En,

embryonic day n;

FITC,

fluorescein isothiocyanate;

Pn,

postnatal day n;

MAP2,

microtubule-associated protein 2