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.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 12 December 2003:
Vol. 302. no. 5652, pp. 1984 - 1988
DOI: 10.1126/science.1089610
Prev | Table of Contents

Reports

Anterior-Posterior Guidance of Commissural Axons by Wnt-Frizzled Signaling

Anna I. Lyuksyutova,2 Chin-Chun Lu,1 Nancy Milanesio,1 Leslie A. King,2 Nini Guo,4 Yanshu Wang,4 Jeremy Nathans,4 Marc Tessier-Lavigne,5* Yimin Zou1,2,3{dagger}

Commissural neurons in the mammalian dorsal spinal cord send axons ventrally toward the floor plate, where they cross the midline and turn anteriorly toward the brain; a gradient of chemoattractant(s) inside the spinal cord controls this turning. In rodents, several Wnt proteins stimulate the extension of commissural axons after midline crossing (postcrossing). We found that Wnt4 messenger RNA is expressed in a decreasing anterior-to-posterior gradient in the floor plate, and that a directed source of Wnt4 protein attracted postcrossing commissural axons. Commissural axons in mice lacking the Wnt receptor Frizzled3 displayed anterior-posterior guidance defects after midline crossing. Thus, Wnt-Frizzled signaling guides commissural axons along the anterior-posterior axis of the spinal cord.

1 Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA.
2 Committee on Developmental Biology, University of Chicago, Chicago, IL 60637, USA.
3 Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.
4 Departments of Molecular Biology and Ophthalmology, Howard Hughes Medical Institute, Johns Hopkins Medical School, Baltimore, MD 21205, USA.
5 Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, CA94305, USA.



* Present address: Genentech Inc., South San Francisco, CA94080, USA.

{dagger} To whom correspondence should be addressed. E-mail: yzou{at}bsd.uchicago.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Axons find their way in the snow.
Y. Zou (2009)
Development 136, 2135-2139
   Abstract »    Full Text »    PDF »
Role of the Atypical Cadherin Celsr3 during Development of the Internal Capsule.
L. Zhou, Y. Qu, F. Tissir, and A. M. Goffinet (2009)
Cereb Cortex 19, i114-i119
   Abstract »    Full Text »    PDF »
Wnt5a Induces Simultaneous Cortical Axon Outgrowth and Repulsive Axon Guidance through Distinct Signaling Mechanisms.
L. Li, B. I. Hutchins, and K. Kalil (2009)
J. Neurosci. 29, 5873-5883
   Abstract »    Full Text »    PDF »
FGF8 Signaling Regulates Growth of Midbrain Dopaminergic Axons by Inducing Semaphorin 3F.
K. Yamauchi, S. Mizushima, A. Tamada, N. Yamamoto, S. Takashima, and F. Murakami (2009)
J. Neurosci. 29, 4044-4055
   Abstract »    Full Text »    PDF »
Pioneer longitudinal axons navigate using floor plate and Slit/Robo signals.
W. T. Farmer, A. L. Altick, H. F. Nural, J. P. Dugan, T. Kidd, F. Charron, and G. S. Mastick (2008)
Development 135, 3643-3653
   Abstract »    Full Text »    PDF »
An essential role for frizzled 5 in mammalian ocular development.
C. Liu and J. Nathans (2008)
Development 135, 3567-3576
   Abstract »    Full Text »    PDF »
Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of {beta}-catenin in mice.
T. Grigoryan, P. Wend, A. Klaus, and W. Birchmeier (2008)
Genes & Dev. 22, 2308-2341
   Abstract »    Full Text »    PDF »
Repulsive Wnt Signaling Inhibits Axon Regeneration after CNS Injury.
Y. Liu, X. Wang, C.-C. Lu, R. Sherman-Kermen, O. Steward, X.-M. Xu, and Y. Zou (2008)
J. Neurosci. 28, 8376-8382
   Abstract »    Full Text »    PDF »
Wnt/{beta}-Catenin Signaling Suppresses Rapsyn Expression and Inhibits Acetylcholine Receptor Clustering at the Neuromuscular Junction.
J. Wang, N.-J. Ruan, L. Qian, W.-l. Lei, F. Chen, and Z.-G. Luo (2008)
J. Biol. Chem. 283, 21668-21675
   Abstract »    Full Text »    PDF »
An Essential Role for Frizzled5 in Neuronal Survival in the Parafascicular Nucleus of the Thalamus.
C. Liu, Y. Wang, P. M. Smallwood, and J. Nathans (2008)
J. Neurosci. 28, 5641-5653
   Abstract »    Full Text »    PDF »
From individual Wnt pathways towards a Wnt signalling network.
H. A Kestler and M. Kuhl (2008)
Phil Trans R Soc B 363, 1333-1347
   Abstract »    Full Text »    PDF »
Wnt-3a and Dickkopf-1 Stimulate Neurite Outgrowth in Ewing Tumor Cells via a Frizzled3- and c-Jun N-Terminal Kinase-Dependent Mechanism.
Y. Endo, E. Beauchamp, D. Woods, W. G. Taylor, J. A. Toretsky, A. Uren, and J. S. Rubin (2008)
Mol. Cell. Biol. 28, 2368-2379
   Abstract »    Full Text »    PDF »
Phosphatidylinositol-3-Kinase-Atypical Protein Kinase C Signaling Is Required for Wnt Attraction and Anterior-Posterior Axon Guidance.
A. M. Wolf, A. I. Lyuksyutova, A. G. Fenstermaker, B. Shafer, C. G. Lo, and Y. Zou (2008)
J. Neurosci. 28, 3456-3467
   Abstract »    Full Text »    PDF »
Wnt3a-mediated chemorepulsion controls movement patterns of cardiac progenitors and requires RhoA function.
Q. Yue, L. Wagstaff, X. Yang, C. Weijer, and A. Munsterberg (2008)
Development 135, 1029-1037
   Abstract »    Full Text »    PDF »
BMP type I receptor complexes have distinct activities mediating cell fate and axon guidance decisions.
K. Yamauchi, K. D. Phan, and S. J. Butler (2008)
Development 135, 1119-1128
   Abstract »    Full Text »    PDF »
WNTers in La Jolla.
S. Y. Sokol and K. A. Wharton Jr (2007)
Development 134, 3393-3399
   Abstract »    Full Text »    PDF »
Genetic contributions to white matter architecture revealed by diffusion tensor imaging in Williams syndrome.
S. Marenco, M. A. Siuta, J. S. Kippenhan, S. Grodofsky, W.-l. Chang, P. Kohn, C. B. Mervis, C. A. Morris, D. R. Weinberger, A. Meyer-Lindenberg, et al. (2007)
PNAS 104, 15117-15122
   Abstract »    Full Text »    PDF »
Wnt Signaling Promotes Regeneration in the Retina of Adult Mammals.
F. Osakada, S. Ooto, T. Akagi, M. Mandai, A. Akaike, and M. Takahashi (2007)
J. Neurosci. 27, 4210-4219
   Abstract »    Full Text »    PDF »
Tissue/planar cell polarity in vertebrates: new insights and new questions.
Y. Wang and J. Nathans (2007)
Development 134, 647-658
   Abstract »    Full Text »    PDF »
Differential requirement for MuSK and dystroglycan in generating patterns of neuromuscular innervation.
J. L. Lefebvre, L. Jing, S. Becaficco, C. Franzini-Armstrong, and M. Granato (2007)
PNAS 104, 2483-2488
   Abstract »    Full Text »    PDF »
Mutational Analysis of Norrin-Frizzled4 Recognition.
P. M. Smallwood, J. Williams, Q. Xu, D. J. Leahy, and J. Nathans (2007)
J. Biol. Chem. 282, 4057-4068
   Abstract »    Full Text »    PDF »
Order from disorder: Self-organization in mammalian hair patterning.
Y. Wang, T. Badea, and J. Nathans (2006)
PNAS 103, 19800-19805
   Abstract »    Full Text »    PDF »
Frizzled/RYK mediated signalling in axon guidance.
P. Bovolenta, J. Rodriguez, and P. Esteve (2006)
Development 133, 4399-4408
   Full Text »    PDF »
Ephrin A/EphA controls the rostral turning polarity of a lateral commissural tract in chick hindbrain..
Y. Zhu, S. Guthrie, and F. Murakami (2006)
Development 133, 3837-3846
   Abstract »    Full Text »    PDF »
Intracellular control of developmental and regenerative axon growth.
F.-Q. Zhou and W. D Snider (2006)
Phil Trans R Soc B 361, 1575-1592
   Abstract »    Full Text »    PDF »
Axon Guidance by Diffusible Chemoattractants: A Gradient of Netrin Protein in the Developing Spinal Cord..
T. E. Kennedy, H. Wang, W. Marshall, and M. Tessier-Lavigne (2006)
J. Neurosci. 26, 8866-8874
   Abstract »    Full Text »    PDF »
The Wnt Receptor Ryk Is Required for Wnt5a-Mediated Axon Guidance on the Contralateral Side of the Corpus Callosum.
T. R. Keeble, M. M. Halford, C. Seaman, N. Kee, M. Macheda, R. B. Anderson, S. A. Stacker, and H. M. Cooper (2006)
J. Neurosci. 26, 5840-5848
   Abstract »    Full Text »    PDF »
PAX2 Activates WNT4 Expression during Mammalian Kidney Development.
E. Torban, A. Dziarmaga, D. Iglesias, L. L. Chu, T. Vassilieva, M. Little, M. Eccles, M. Discenza, J. Pelletier, and P. Goodyer (2006)
J. Biol. Chem. 281, 12705-12712
   Abstract »    Full Text »    PDF »
Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans.
B. C. Prasad and S. G. Clark (2006)
Development 133, 1757-1766
   Abstract »    Full Text »    PDF »
Activity-dependent Synaptic Wnt Release Regulates Hippocampal Long Term Potentiation.
J. Chen, C. S. Park, and S.-J. Tang (2006)
J. Biol. Chem. 281, 11910-11916
   Abstract »    Full Text »    PDF »
Phosphorylation of Frizzled-3.
W. A. Yanfeng, C. Tan, R. J. Fagan, and P. S. Klein (2006)
J. Biol. Chem. 281, 11603-11609
   Abstract »    Full Text »    PDF »
The role of Frizzled3 and Frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells..
Y. Wang, N. Guo, and J. Nathans (2006)
J. Neurosci. 26, 2147-2156
   Abstract »    Full Text »    PDF »
Axonal Growth and Guidance Defects in Frizzled3 Knock-Out Mice: A Comparison of Diffusion Tensor Magnetic Resonance Imaging, Neurofilament Staining, and Genetically Directed Cell Labeling.
Y. Wang, J. Zhang, S. Mori, and J. Nathans (2006)
J. Neurosci. 26, 355-364
   Abstract »    Full Text »    PDF »
Neurite outgrowth involves adenomatous polyposis coli protein and {beta}-catenin.
V. Votin, W. J. Nelson, and A. I. M. Barth (2005)
J. Cell Sci. 118, 5699-5708
   Abstract »    Full Text »    PDF »
Wnt Signaling in Neural Circuit Development.
L. G. Fradkin, G. Garriga, P. C. Salinas, J. B. Thomas, X. Yu, and Y. Zou (2005)
J. Neurosci. 25, 10376-10378
   Full Text »    PDF »
Sensitized genetic backgrounds reveal a role for C. elegans FGF EGL-17 as a repellent for migrating CAN neurons.
T. C. Fleming, F. W. Wolf, and G. Garriga (2005)
Development 132, 4857-4867
   Abstract »    Full Text »    PDF »
Negative regulation of retinal-neurite extension by {beta}-catenin signaling pathway.
Y. Ouchi, Y. Tabata, K.-i. Arai, and S. Watanabe (2005)
J. Cell Sci. 118, 4473-4483
   Abstract »    Full Text »    PDF »
Attenuated Wnt Signaling Perturbs Pancreatic Growth but Not Pancreatic Function.
S. Papadopoulou and H. Edlund (2005)
Diabetes 54, 2844-2851
   Abstract »    Full Text »    PDF »
Wnt signaling drives WRM-1/{beta}-catenin asymmetries in early C. elegans embryos.
K. Nakamura, S. Kim, T. Ishidate, Y. Bei, K. Pang, M. Shirayama, C. Trzepacz, D. R. Brownell, and C. C. Mello (2005)
Genes & Dev. 19, 1749-1754
   Abstract »    Full Text »    PDF »
Novel brain wiring functions for classical morphogens: a role as graded positional cues in axon guidance.
F. Charron and M. Tessier-Lavigne (2005)
Development 132, 2251-2262
   Abstract »    Full Text »    PDF »
Sonic Hedgehog Has a Dual Effect on the Growth of Retinal Ganglion Axons Depending on Its Concentration.
A. Kolpak, J. Zhang, and Z.-Z. Bao (2005)
J. Neurosci. 25, 3432-3441
   Abstract »    Full Text »    PDF »
Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgf{beta}1 regulate semaphorin 3a expression in the dental mesenchyme.
P. Kettunen, S. Loes, T. Furmanek, K. Fjeld, I. H. Kvinnsland, O. Behar, T. Yagi, H. Fujisawa, S. Vainio, M. Taniguchi, et al. (2005)
Development 132, 323-334
   Abstract »    Full Text »    PDF »
Ryk: Another Heretical Wnt Receptor Defies the Canon.
B. N. R. Cheyette (2004)
Sci. STKE 2004, pe54
   Abstract »    Full Text »    PDF »
The conserved kinase UNC-51 acts with VAB-8 and UNC-14 to regulate axon outgrowth in C. elegans.
T. Lai and G. Garriga (2004)
Development 131, 5991-6000
   Abstract »    Full Text »    PDF »
The Caenorhabditis elegans Ror RTK CAM-1 Inhibits EGL-20/Wnt Signaling in Cell Migration.
W. C. Forrester, C. Kim, and G. Garriga (2004)
Genetics 168, 1951-1962
   Abstract »    Full Text »    PDF »
Hedgehog and Decapentaplegic instruct polarized growth of cell extensions in the Drosophila trachea.
K. Kato, T. Chihara, and S. Hayashi (2004)
Development 131, 5253-5261
   Abstract »    Full Text »    PDF »
From The Cover: Frizzled6 controls hair patterning in mice.
N. Guo, C. Hawkins, and J. Nathans (2004)
PNAS 101, 9277-9281
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)