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 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.
Nakajima
K
K
Molecular Neurobiology Laboratory, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Tsukuba, Ibaraki 305, Japan. nakjima@rtc.riken.go.jp
Mikoshiba
K
K
Miyata
T
T
Kudo
C
C
Ogawa
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D006624:Hippocampus / Q000196:embryology* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins; D010641:Phenotype; D011247:Pregnancy; D000091042:Reelin Protein; D012697:Serine Endopeptidases
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases