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The Journal of Neuroscience, August 26, 2009, 29(34):10653-10662; doi:10.1523/JNEUROSCI.0345-09.2009

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Development/Plasticity/Repair
Downregulation of Functional Reelin Receptors in Projection Neurons Implies That Primary Reelin Action Occurs atEarly/Premigratory Stages

Takayuki Uchida,¹ Atsushi Baba,¹ F. Javier Pérez-Martínez,² Terumasa Hibi,¹ Takaki Miyata,³ Juan M. Luque,² Kazunori Nakajima,⁴ and Mitsuharu Hattori¹

¹Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Aichi 467-8603, Japan, ²Laboratory of Molecular Neuroanatomy, Instituto de Neurociencias, University Miguel Hernandez-Consejo Superior de Investigaciones Cientificas, San Juan de Alicante, E-03550, Spain, ³Department of Anatomy and Cell Biology, Nagoya University School of Medicine, Showa-ku, Nagoya, Aichi 466-8550, Japan, and ⁴Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan

Correspondence should be addressed to Mitsuharu Hattori, Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. Email: mhattori{at}phar.nagoya-cu.ac.jp

Reelin signaling is essential for correct development of the mammalian brain. Reelin binds to apolipoprotein E receptor 2 and very low-density lipoprotein receptor and induces phosphorylation of Dab1. However, when and where these reactions occur is essentially unknown, and the primary function(s) of Reelin remain unclear.

Here, we used alkaline phosphatase fusion of the receptor-binding region of Reelin to quantitatively investigate the localization of functional Reelin receptors (i.e., those on the plasma membrane as mature forms) in the developing brain. In the wild-type cerebral cortex, they are mainly present in the intermediate and subventricular zones, as well as in radial fibers, but much less in the cell bodies of the cortical plate. Functional Reelin receptors are much more abundant in the Reelin-deficient cortical plate, indicating that Reelin induces their downregulation and that it begins before the neurons migrate out of the intermediate zone. In the wild-type cerebellum, functional Reelin receptors are mainly present in the cerebellar ventricular zone but scarcely expressed by Purkinje cells that have migrated out of it. It is thus strongly suggested that Reelin exerts critical actions on migrating projection neurons at their early/premigratory stages en route to their final destinations, in the developing cerebral cortex and cerebellum.

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Received Jan. 22, 2009; revised July 1, 2009; accepted July 21, 2009.

Correspondence should be addressed to Mitsuharu Hattori, Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. Email: mhattori{at}phar.nagoya-cu.ac.jp

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