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The Journal of Neuroscience, December 20, 2006, 26(51):13357-13362; doi:10.1523/JNEUROSCI.4276-06.2006

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Brief Communications
Collapsin Response Mediator Protein 1 Mediates Reelin Signaling in Cortical Neuronal Migration

Naoya Yamashita,¹ Yutaka Uchida,¹ Toshio Ohshima,⁴ Syu-ichi Hirai,² Fumio Nakamura,¹ Masahiko Taniguchi,⁵ Katsuhiko Mikoshiba,⁴ Jérôme Honnorat,⁶ Pappachan Kolattukudy,⁷ Nicole Thomasset,⁶ Kohtaro Takei,^1,8 Takuya Takahashi,³ and Yoshio Goshima^1,8

Departments of ¹Molecular Pharmacology and Neurobiology, ²Molecular Biology, and ³Physiology and Neuroendocrinology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan, ⁴Laboratory for Developmental Neurobiology, Brain Science Institute, The Institute of Physical and Chemical Research, Wako 351-0198, Japan, ⁵Department of Biochemistry, Cancer Research Institute, Sapporo Medical University, Sapporo 060-8556, Japan, ⁶Institut National de la Santé et de la Recherche Médicale Unité 433, Institut Federatif des Neurosciences de Lyon, Hôpital Neurologique, F-69003 Lyon, France, ⁷Biomolecular Science Center, University of Central Florida, Biomolecular Science, Orlando, Florida 32816, and ⁸Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan

Correspondence should be addressed to Yoshio Goshima, Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Fuku-ura 3-9, Kanazawa Ward, Yokohama City 236-0004, Japan. Email: goshima{at}med.yokohama-cu.ac.jp

Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that mediates signal transduction of axon guidance molecules. Here, we show evidence that CRMP1 is involved in Reelin (Reln) signaling to regulate neuronal migration in the cerebral cortex. In crmp1^–/– mice, radial migration of cortical neurons was retarded. This phenotype was not observed in the sema3A^–/– and crmp1^+/–;sema3A^+/– cortices. However, CRMP1 was colocalized with disabled-1 (Dab1), an adaptor protein in Reln signaling. In the Reln^rl/rl cortex, CRMP1 and Dab1 were expressed at a higher level, yet tyrosine phosphorylated at a lower level. Loss of crmp1 in a dab1 heterozygous background led to the disruption of hippocampal lamination, a Reeler-like phenotype. In addition to axon guidance, CRMP1 regulates neuronal migration by mediating Reln signaling.

Key words: CRMP; Reln; Dab1; tyrosine phosphorylation; neuronal migration; cerebral cortex

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Received Sept. 30, 2006; revised Nov. 15, 2006; accepted Nov. 17, 2006.

Correspondence should be addressed to Yoshio Goshima, Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Fuku-ura 3-9, Kanazawa Ward, Yokohama City 236-0004, Japan. Email: goshima{at}med.yokohama-cu.ac.jp

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