Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Netrin-DCC Signaling Regulates Corpus Callosum Formation Through Attraction of Pioneering Axons and by Modulating Slit2-Mediated Repulsion.
T. Fothergill, A.-L. S. Donahoo, A. Douglass, O. Zalucki, J. Yuan, T. Shu, G. J. Goodhill, and L. J. Richards (2013)
Cereb Cortex
   Abstract »    Full Text »    PDF »
N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors.
Q. Chen, X. Sun, X.-h. Zhou, J.-h. Liu, J. Wu, Y. Zhang, and J.-h. Wang (2013)
J. Cell Sci. 126, 186-195
   Abstract »    Full Text »    PDF »
Down Syndrome Cell Adhesion Molecule (DSCAM) Associates with Uncoordinated-5C (UNC5C) in Netrin-1-mediated Growth Cone Collapse.
A. A. Purohit, W. Li, C. Qu, T. Dwyer, Q. Shao, K.-L. Guan, and G. Liu (2012)
J. Biol. Chem. 287, 27126-27138
   Abstract »    Full Text »    PDF »
Wnt-Induced Calcium Signaling Mediates Axon Growth and Guidance in the Developing Corpus Callosum.
B. I. Hutchins, L. Li, and K. Kalil (2012)
Science Signaling 5, pt1
   Abstract »    Full Text »    PDF »
Draxin Inhibits Axonal Outgrowth through the Netrin Receptor DCC.
G. Ahmed, Y. Shinmyo, K. Ohta, S. M. Islam, M. Hossain, I. B. Naser, M. A. Riyadh, Y. Su, S. Zhang, M. Tessier-Lavigne, et al. (2011)
J. Neurosci. 31, 14018-14023
   Abstract »    Full Text »    PDF »
Heparan Sulfate Sugar Modifications Mediate the Functions of Slits and Other Factors Needed for Mouse Forebrain Commissure Development.
C. D. Conway, K. M. Howe, N. K. Nettleton, D. J. Price, J. O. Mason, and T. Pratt (2011)
J. Neurosci. 31, 1955-1970
   Abstract »    Full Text »    PDF »
Navigating Intermediate Targets: The Nervous System Midline.
B. J. Dickson and Y. Zou (2010)
Cold Spring Harb Perspect Biol 2, a002055
   Abstract »    Full Text »    PDF »
Wiring the Brain: The Biology of Neuronal Guidance.
A. Chedotal and L. J. Richards (2010)
Cold Spring Harb Perspect Biol 2, a001917
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882