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The Journal of Neuroscience, February 15, 1999, 19(4):1345-1358
Reelin Regulates the Development and Synaptogenesis of the Layer-Specific Entorhino-Hippocampal Connections
Víctor Borrell1, José A. Del Río1, Soledad Alcántara1, Michèle Derer2, Albert Martínez1, Gabriella D'Arcangelo3, Kazunori Nakajima4, Katsuhiko Mikoshiba5, Paul Derer2, Tom Curran3, and Eduardo Soriano1 1 Department of Animal and Plant Cell Biology, University of Barcelona, Barcelona 08028, Spain, 2 Developmental Neurobiology Laboratory, Pierre et Marie Curie University, Paris 75005, France, 3 Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, 4 Department of Molecular Neurobiology, Institute of DNA Medicine, Research Center for Medical Science, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan, and 5 Department of Molecular Neurobiology, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
Here we examine the role of Reelin, an extracellular protein involved in neuronal migration, in the formation of hippocampal connections. Both at prenatal and postnatal stages, the general laminar and topographic distribution of entorhinal projections is preserved in the hippocampus of reeler mutant mice, in the absence of Reelin. However, developing and adult entorhinal afferents show severe alterations, including increased numbers of misrouted fibers and the formation of abnormal patches of termination from the medial and lateral entorhinal cortices. At perinatal stages, single entorhinal axons in reeler mice are grouped into thick bundles, and they have decreased axonal branching and decreased extension of axon collaterals. We also show that the number of entorhino-hippocampal synapses is lower in reeler mice than in control animals during development. Studies performed in mixed entorhino-hippocampal co-cultures combining slices from reeler and wild-type mice indicate that these abnormalities are caused by the lack of Reelin in the target hippocampus. These findings imply that Reelin fulfills a modulatory role during the formation of layer-specific and topographic connections in the hippocampus. They also suggest that Reelin promotes maturation of single fibers and synaptogenesis by entorhinal afferents.
Key words: Reelin; Cajal-Retzius cells; synaptic specificity; neuronal connections; hippocampus; reeler mutant mouse
Copyright © 1999 Society for Neuroscience 0270-6474/99/1941345-14$05.00/0
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