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Science 323 (5912): 388-393

Copyright © 2009 by the American Association for the Advancement of Science

Draxin, a Repulsive Guidance Protein for Spinal Cord and Forebrain Commissures

Shahidul M. Islam,1,2* Yohei Shinmyo,1,2* Tatsuya Okafuji,1{dagger} Yuhong Su,1,2,3 Iftekhar Bin Naser,1,2,3 Giasuddin Ahmed,1,2,3 Sanbing Zhang,1,2,3 Sandy Chen,1 Kunimasa Ohta,1 Hiroshi Kiyonari,4 Takaya Abe,4 Satomi Tanaka,5 Ryuichi Nishinakamura,3,5 Toshio Terashima,6 Toshio Kitamura,7 Hideaki Tanaka1,2,3{ddagger}

Abstract: Axon guidance proteins are critical for the correct wiring of the nervous system during development. Several axon guidance cues and their family members have been well characterized. More unidentified axon guidance cues are assumed to participate in the formation of the extremely complex nervous system. We identified a secreted protein, draxin, that shares no homology with known guidance cues. Draxin inhibited or repelled neurite outgrowth from dorsal spinal cord and cortical explants in vitro. Ectopically expressed draxin inhibited growth or caused misrouting of chick spinal cord commissural axons in vivo. draxin knockout mice showed defasciculation of spinal cord commissural axons and absence of all forebrain commissures. Thus, draxin is a previously unknown chemorepulsive axon guidance molecule required for the development of spinal cord and forebrain commissures.

1 Division of Developmental Neurobiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
2 21st Century COE (Center of Excellence) Cell Fate Regulation Research and Education Unit, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
3 Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
4 Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
5 Division of Integrative Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
6 Division of Anatomy and Neurobiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
7 Division of Cellular Therapy, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

* These authors contributed equally to this work.

{dagger} Present address: Department of Genetics, Trinity College Dublin, Dublin 2, Ireland.

{ddagger} To whom correspondence should be addressed. E-mail: hitanaka{at}kumamoto-u.ac.jp

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