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.
Annual Meeting

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 6 December 2002:
Vol. 298. no. 5600, pp. 1959 - 1964
DOI: 10.1126/science.1072165
Prev | Table of Contents | Next

Review

Molecular Mechanisms of Axon Guidance

Barry J. Dickson

Axons are guided along specific pathways by attractive and repulsive cues in the extracellular environment. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules, including netrins, Slits, semaphorins, and ephrins. Guidance cues steer axons by regulating cytoskeletal dynamics in the growth cone through signaling pathways that are still only poorly understood. Elaborate regulatory mechanisms ensure that a given cue elicits the right response from the right axons at the right time but is otherwise ignored. With such regulatory mechanisms in place, a relatively small number of guidance factors can be used to generate intricate patterns of neuronal wiring.

Research Institute of Molecular Pathology, Dr. Bohr-gasse 7, A-1030 Vienna, Austria. E-mail: dickson{at}nt.imp.univie.ac.at

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Novel Regulated Expression of the SLIT/ROBO Pathway in the Ovary: Possible Role during Luteolysis in Women.
R. E. Dickinson, M. Myers, and W. C. Duncan (2008)
Endocrinology 149, 5024-5034
   Abstract »    Full Text »    PDF »
Rho inhibition recruits DCC to the neuronal plasma membrane and enhances axon chemoattraction to netrin 1.
S. W. Moore, J. P. Correia, K. Lai Wing Sun, M. Pool, A. E. Fournier, and T. E. Kennedy (2008)
Development 135, 2855-2864
   Abstract »    Full Text »    PDF »
Pathfinding in a large vertebrate axon tract: isotypic interactions guide retinotectal axons at multiple choice points.
A. J. Pittman, M.-Y. Law, and C.-B. Chien (2008)
Development 135, 2865-2871
   Abstract »    Full Text »    PDF »
Specificity of Afferent Synapses onto Plane-Polarized Hair Cells in the Posterior Lateral Line of the Zebrafish.
A. Nagiel, D. Andor-Ardo, and A. J. Hudspeth (2008)
J. Neurosci. 28, 8442-8453
   Abstract »    Full Text »    PDF »
Src family kinases are required for WNT5 signaling through the Derailed/RYK receptor in the Drosophila embryonic central nervous system.
R. R. Wouda, M. R. K. S. Bansraj, A. W. M. de Jong, J. N. Noordermeer, and L. G. Fradkin (2008)
Development 135, 2277-2287
   Abstract »    Full Text »    PDF »
Molecular Mechanisms Controlling Midline Crossing by Precerebellar Neurons.
T. Di Meglio, K. T. Nguyen-Ba-Charvet, M. Tessier-Lavigne, C. Sotelo, and A. Chedotal (2008)
J. Neurosci. 28, 6285-6294
   Abstract »    Full Text »    PDF »
Structural and Functional Analysis of Slit and Heparin Binding to Immunoglobulin-like Domains 1 and 2 of Drosophila Robo.
N. Fukuhara, J. A. Howitt, S.-A. Hussain, and E. Hohenester (2008)
J. Biol. Chem. 283, 16226-16234
   Abstract »    Full Text »    PDF »
Synaptic Patterning by Morphogen Signaling.
W. R. Williamson and P. R. Hiesinger (2008)
Science Signaling 1, pe20
   Abstract »    Full Text »    PDF »
CLEC-38, A Transmembrane Protein with C-Type Lectin-Like Domains, Negatively Regulates UNC-40-Mediated Axon Outgrowth and Promotes Presynaptic Development in Caenorhabditis elegans.
G. Kulkarni, H. Li, and W. G. Wadsworth (2008)
J. Neurosci. 28, 4541-4550
   Abstract »    Full Text »    PDF »
The Protein Dendrite Arborization and Synapse Maturation 1 (Dasm-1) Is Dispensable for Dendrite Arborization.
A. Mishra, B. Knerr, S. Paixao, E. R. Kramer, and R. Klein (2008)
Mol. Cell. Biol. 28, 2782-2791
   Abstract »    Full Text »    PDF »
RPM-1, a Caenorhabditis elegans Protein That Functions in Presynaptic Differentiation, Negatively Regulates Axon Outgrowth by Controlling SAX-3/robo and UNC-5/UNC5 Activity.
H. Li, G. Kulkarni, and W. G. Wadsworth (2008)
J. Neurosci. 28, 3595-3603
   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 »
A Cytoskeletal Platform for Local Translation in Axons.
F. P. G. Van Horck and C. E. Holt (2008)
Science Signaling 1, pe11
   Abstract »    Full Text »    PDF »
TGF{beta}-Smad2 Signaling Regulates the Cdh1-APC/SnoN Pathway of Axonal Morphogenesis.
J. Stegmuller, M. A. Huynh, Z. Yuan, Y. Konishi, and A. Bonni (2008)
J. Neurosci. 28, 1961-1969
   Abstract »    Full Text »    PDF »
Identification of Motifs That Are Conserved in 12 Drosophila Species and Regulate Midline Glia vs. Neuron Expression.
P. Estes, E. Fulkerson, and Y. Zhang (2008)
Genetics 178, 787-799
   Abstract »    Full Text »    PDF »
A role for S1P signalling in axon guidance in the Xenopus visual system.
L. Strochlic, A. Dwivedy, F. P. G. van Horck, J. Falk, and C. E. Holt (2008)
Development 135, 333-342
   Abstract »    Full Text »    PDF »
FGF signals guide migration of mesenchymal cells, control skeletal morphogenesis and regulate gastrulation during sea urchin development.
E. Rottinger, A. Saudemont, V. Duboc, L. Besnardeau, D. McClay, and T. Lepage (2008)
Development 135, 353-365
   Abstract »    Full Text »    PDF »
Matrix metalloproteinases promote motor axon fasciculation in the Drosophila embryo.
C. M. Miller, A. Page-McCaw, and H. T. Broihier (2008)
Development 135, 95-109
   Abstract »    Full Text »    PDF »
Cytoplasmic domain requirements for Frazzled-mediated attractive axon turning at the Drosophila midline.
D. S. Garbe, M. O'Donnell, and G. J. Bashaw (2007)
Development 134, 4325-4334
   Abstract »    Full Text »    PDF »
Spinal Cord Injury: Time to Move?.
S. Rossignol, M. Schwab, M. Schwartz, and M. G. Fehlings (2007)
J. Neurosci. 27, 11782-11792
   Abstract »    Full Text »    PDF »
BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin.
Z. Wen, L. Han, J. R. Bamburg, S. Shim, G.-l. Ming, and J. Q. Zheng (2007)
J. Cell Biol. 178, 107-119
   Abstract »    Full Text »    PDF »
Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis.
B. Larrivee, C. Freitas, M. Trombe, X. Lv, B. DeLafarge, L. Yuan, K. Bouvree, C. Breant, R. Del Toro, N. Brechot, et al. (2007)
Genes & Dev. 21, 2433-2447
   Abstract »    Full Text »    PDF »
Analysis of zebrafish sidetracked mutants reveals a novel role for Plexin A3 in intraspinal motor axon guidance.
K. A. Palaisa and M. Granato (2007)
Development 134, 3251-3257
   Abstract »    Full Text »    PDF »
Targeting of Retinal Axons Requires the Metalloproteinase ADAM10.
Y. Chen, C. L. Hehr, K. Atkinson-Leadbeater, J. C. Hocking, and S. McFarlane (2007)
J. Neurosci. 27, 8448-8456
   Abstract »    Full Text »    PDF »
Functional Interaction between Matrix Metalloproteinase-3 and Semaphorin-3C during Cortical Axonal Growth and Guidance.
B Gonthier, C Nasarre, L Roth, M Perraut, N Thomasset, G Roussel, D Aunis, and D Bagnard (2007)
Cereb Cortex 17, 1712-1721
   Abstract »    Full Text »    PDF »
Dual Branch-Promoting and Branch-Repelling Actions of Slit/Robo Signaling on Peripheral and Central Branches of Developing Sensory Axons.
L. Ma and M. Tessier-Lavigne (2007)
J. Neurosci. 27, 6843-6851
   Abstract »    Full Text »    PDF »
Crk-associated substrate (Cas) signaling protein functions with integrins to specify axon guidance during development.
Z. Huang, U. Yazdani, K. L. Thompson-Peer, A. L. Kolodkin, and J. R. Terman (2007)
Development 134, 2337-2347
   Abstract »    Full Text »    PDF »
Localized VEGF signaling from ectoderm to mesenchyme cells controls morphogenesis of the sea urchin embryo skeleton.
L. Duloquin, G. Lhomond, and C. Gache (2007)
Development 134, 2293-2302
   Abstract »    Full Text »    PDF »
Targeting Sensory Axon Regeneration in Adult Spinal Cord.
X.-Q. Tang, P. Heron, C. Mashburn, and G. M. Smith (2007)
J. Neurosci. 27, 6068-6078
   Abstract »    Full Text »    PDF »
Multiple Effects of Ephrin-A5 on Cortical Neurons Are Mediated by Src Family Kinases.
G. Zimmer, B. Kastner, F. Weth, and J. Bolz (2007)
J. Neurosci. 27, 5643-5653
   Abstract »    Full Text »    PDF »
Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration.
A. S. Novgorodov, M. El-Alwani, J. Bielawski, L. M. Obeid, and T. I. Gudz (2007)
FASEB J 21, 1503-1514
   Abstract »    Full Text »    PDF »
The F-actin-microtubule crosslinker Shot is a platform for Krasavietz-mediated translational regulation of midline axon repulsion.
S. Lee, M. Nahm, M. Lee, M. Kwon, E. Kim, A. D. Zadeh, H. Cao, H.-J. Kim, Z. H. Lee, S. B. Oh, et al. (2007)
Development 134, 1767-1777
   Abstract »    Full Text »    PDF »
CXC chemokine receptor 4 regulates neuronal migration and axonal pathfinding in the developing nervous system: implications for neuronal regeneration in the adult brain.
R. Stumm and V. Hollt (2007)
J. Mol. Endocrinol. 38, 377-382
   Abstract »    Full Text »    PDF »
Distinct functions of {alpha}-Spectrin and {beta}-Spectrin during axonal pathfinding.
J. Hulsmeier, J. Pielage, C. Rickert, G. M. Technau, C. Klambt, and T. Stork (2007)
Development 134, 713-722
   Abstract »    Full Text »    PDF »
Getting axons onto the right path: the role of transcription factors in axon guidance.
S. J. Butler and G. Tear (2007)
Development 134, 439-448
   Abstract »    Full Text »    PDF »
Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126).
C. Schmitz, P. Kinge, and H. Hutter (2007)
PNAS 104, 834-839
   Abstract »    Full Text »    PDF »
Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP.
J. Han, L. Han, P. Tiwari, Z. Wen, and J. Q. Zheng (2007)
J. Cell Biol. 176, 101-111
   Abstract »    Full Text »    PDF »
Ptpmeg is required for the proper establishment and maintenance of axon projections in the central brain of Drosophila.
J. L. Whited, M. B. Robichaux, J. C. Yang, and P. A. Garrity (2007)
Development 134, 43-53
   Abstract »    Full Text »    PDF »
A Molecular Mechanism for the Heparan Sulfate Dependence of Slit-Robo Signaling.
S.-A. Hussain, M. Piper, N. Fukuhara, L. Strochlic, G. Cho, J. A. Howitt, Y. Ahmed, A. K. Powell, J. E. Turnbull, C. E. Holt, et al. (2006)
J. Biol. Chem. 281, 39693-39698
   Abstract »    Full Text »    PDF »
Netrin/DCC Signaling Controls Contralateral Dendrites of Octavolateralis Efferent Neurons.
A. Suli, N. Mortimer, I. Shepherd, and C.-B. Chien (2006)
J. Neurosci. 26, 13328-13337
   Abstract »    Full Text »    PDF »
GABA Regulates Dendritic Growth by Stabilizing Lamellipodia in Newly Generated Interneurons of the Olfactory Bulb.
E. Gascon, A. G. Dayer, M.-O. Sauvain, G. Potter, B. Jenny, M. De Roo, E. Zgraggen, N. Demaurex, D. Muller, and J. Z. Kiss (2006)
J. Neurosci. 26, 12956-12966
   Abstract »    Full Text »    PDF »
Increasing the Frequency of Spontaneous Rhythmic Activity Disrupts Pool-Specific Axon Fasciculation and Pathfinding of Embryonic Spinal Motoneurons.
M. G. Hanson and L. T. Landmesser (2006)
J. Neurosci. 26, 12769-12780
   Abstract »    Full Text »    PDF »
The metalloprotease Tolloid-related and its TGF-{beta}-like substrate Dawdle regulate Drosophila motoneuron axon guidance..
M. Serpe and M. B. O'Connor (2006)
Development 133, 4969-4979
   Abstract »    Full Text »    PDF »
The divergent TGF-{beta} ligand Dawdle utilizes an activin pathway to influence axon guidance in Drosophila..
L. Parker, J. E. Ellis, M. Q. Nguyen, and K. Arora (2006)
Development 133, 4981-4991
   Abstract »    Full Text »    PDF »
SWAN-1, a Caenorhabditis elegans WD Repeat Protein of the AN11 Family, Is a Negative Regulator of Rac GTPase Function.
Y. Yang, J. Lu, J. Rovnak, S. L. Quackenbush, and E. A. Lundquist (2006)
Genetics 174, 1917-1932
   Abstract »    Full Text »    PDF »
CD47 Promotes Neuronal Development through Src- and FRG/Vav2-Mediated Activation of Rac and Cdc42.
T. Murata, H. Ohnishi, H. Okazawa, Y. Murata, S. Kusakari, Y. Hayashi, M. Miyashita, H. Itoh, P.-A. Oldenborg, N. Furuya, et al. (2006)
J. Neurosci. 26, 12397-12407
   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 »
The Caenorhabditis elegans P21-activated kinases are differentially required for UNC-6/netrin-mediated commissural motor axon guidance.
M. Lucanic, M. Kiley, N. Ashcroft, N. L'Etoile, and H.-J. Cheng (2006)
Development 133, 4549-4559
   Abstract »    Full Text »    PDF »
COUP-TFI is required for the formation of commissural projections in the forebrain by regulating axonal growth.
M. Armentano, A. Filosa, G. Andolfi, and M. Studer (2006)
Development 133, 4151-4162
   Abstract »    Full Text »    PDF »
Axon Pruning and Synaptic Development: How Are They per-Plexin?.
K. E. Waimey and H.-J. Cheng (2006)
Neuroscientist 12, 398-409
   Abstract »    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 »
The autophagy-related kinase UNC-51 and its binding partner UNC-14 regulate the subcellular localization of the Netrin receptor UNC-5 in Caenorhabditis elegans.
K.-i. Ogura and Y. Goshima (2006)
Development 133, 3441-3450
   Abstract »    Full Text »    PDF »
Individual cell migration serves as the driving force for optic vesicle evagination..
M. Rembold, F. Loosli, R. J. Adams, and J. Wittbrodt (2006)
Science 313, 1130-1134
   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 »
Growth cone navigation in substrate-bound ephrin gradients.
A. C. von Philipsborn, S. Lang, J. Loeschinger, A. Bernard, C. David, D. Lehnert, F. Bonhoeffer, and M. Bastmeyer (2006)
Development 133, 2487-2495
   Abstract »    Full Text »    PDF »
Genes That Control Ray Sensory Neuron Axon Development in the Caenorhabditis elegans Male.
L. Jia and S. W. Emmons (2006)
Genetics 173, 1241-1258
   Abstract »    Full Text »    PDF »
Heparan sulphation patterns generated by specific heparan sulfotransferase enzymes direct distinct aspects of retinal axon guidance at the optic chiasm..
T. Pratt, C. D. Conway, N. M. M.-L. Tian, D. J. Price, and J. O. Mason (2006)
J. Neurosci. 26, 6911-6923
   Abstract »    Full Text »    PDF »
Drosophila Plexin B is a Sema-2a receptor required for axon guidance.
J. C. Ayoob, J. R. Terman, and A. L. Kolodkin (2006)
Development 133, 2125-2135
   Abstract »    Full Text »    PDF »
Robo4 Signaling in Endothelial Cells Implies Attraction Guidance Mechanisms.
S. Kaur, M. D. Castellone, V. M. Bedell, M. Konar, J. S. Gutkind, and R. Ramchandran (2006)
J. Biol. Chem. 281, 11347-11356
   Abstract »    Full Text »    PDF »
Identification of novel mutations in the SEMA4A gene associated with retinal degenerative diseases.
A Abid, M Ismail, S Q Mehdi, and S Khaliq (2006)
J. Med. Genet. 43, 378-381
   Abstract »    Full Text »    PDF »
FGF negatively regulates muscle membrane extension in Caenorhabditis elegans.
S. J. Dixon, M. Alexander, R. Fernandes, N. Ricker, and P. J. Roy (2006)
Development 133, 1263-1275
   Abstract »    Full Text »    PDF »
Wiring optimization can relate neuronal structure and function.
B. L. Chen, D. H. Hall, and D. B. Chklovskii (2006)
PNAS 103, 4723-4728
   Abstract »    Full Text »    PDF »
The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in the Drosophila visual system.
D. Umetsu, S. Murakami, M. Sato, and T. Tabata (2006)
Development 133, 791-800
   Abstract »    Full Text »    PDF »
Vascular endothelial-derived semaphorin 3 inhibits sympathetic axon growth.
D. H. Damon (2006)
Am J Physiol Heart Circ Physiol 290, H1220-H1225
   Abstract »    Full Text »    PDF »
Cdc42 and Actin Control Polarized Expression of TI-VAMP Vesicles to Neuronal Growth Cones and Their Fusion with the Plasma Membrane.
P. Alberts, R. Rudge, T. Irinopoulou, L. Danglot, C. Gauthier-Rouviere, and T. Galli (2006)
Mol. Biol. Cell 17, 1194-1203
   Abstract »    Full Text »    PDF »
belladonna/(lhx2) is required for neural patterning and midline axon guidance in the zebrafish forebrain.
A. Seth, J. Culverwell, M. Walkowicz, S. Toro, J. M. Rick, S. C. F. Neuhauss, Z. M. Varga, and R. O. Karlstrom (2006)
Development 133, 725-735
   Abstract »    Full Text »    PDF »
Interactions of UNC-34 Enabled With Rac GTPases and the NIK Kinase MIG-15 in Caenorhabditis elegans Axon Pathfinding and Neuronal Migration.
M. A. Shakir, J. S. Gill, and E. A. Lundquist (2006)
Genetics 172, 893-913
   Abstract »    Full Text »    PDF »
The Inositol Polyphosphate 5-Phosphatase, PIPP, Is a Novel Regulator of Phosphoinositide 3-Kinase-dependent Neurite Elongation.
L. M. Ooms, C. G. Fedele, M. V. Astle, I. Ivetac, V. Cheung, R. B. Pearson, M. J. Layton, A. Forrai, H. H. Nandurkar, and C. A. Mitchell (2006)
Mol. Biol. Cell 17, 607-622
   Abstract »    Full Text »    PDF »
Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain.
S. W. Mendes, M. Henkemeyer, and D. J. Liebl (2006)
J. Neurosci. 26, 882-892
   Abstract »    Full Text »    PDF »
Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion.
F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann (2006)
Physiol Rev 86, 1-23
   Abstract »    Full Text »    PDF »
Molecular Control of Spinal Accessory Motor Neuron/Axon Development in the Mouse Spinal Cord.
A. K. Dillon, S. C. Fujita, M. P. Matise, A. A. Jarjour, T. E. Kennedy, H. Kollmus, H.-H. Arnold, J. A. Weiner, J. R. Sanes, and Z. Kaprielian (2005)
J. Neurosci. 25, 10119-10130
   Abstract »    Full Text »    PDF »
Adaptation is not required to explain the long-term response of axons to molecular gradients.
J. Xu, W. J. Rosoff, J. S. Urbach, and G. J. Goodhill (2005)
Development 132, 4545-4552
   Abstract »    Full Text »    PDF »
The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones.
B. Tursun, A. Schluter, M. A. Peters, B. Viehweger, H. P. Ostendorff, J. Soosairajah, A. Drung, M. Bossenz, S. A. Johnsen, M. Schweizer, et al. (2005)
Genes & Dev. 19, 2307-2319
   Abstract »    Full Text »    PDF »
A Molecular Model for Axon Guidance Based on Cross Talk between Rho GTPases.
Y. Sakumura, Y. Tsukada, N. Yamamoto, and S. Ishii (2005)
Biophys. J. 89, 812-822
   Abstract »    Full Text »    PDF »
Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth.
M. D. Benson, M. I. Romero, M. E. Lush, Q. R. Lu, M. Henkemeyer, and L. F. Parada (2005)
PNAS 102, 10694-10699
   Abstract »    Full Text »    PDF »
N