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.
Glia Promote Local Synaptogenesis Through UNC-6 (Netrin) Signaling in C. elegans
Daniel A. Colón-Ramos,1
Milica A. Margeta,12
Kang Shen12*
Abstract:
Neural circuits are assembled through the coordinated innervation of pre- and postsynaptic partners. We show that connectivity between two interneurons, AIY and RIA, in Caenorhabditis elegans is orchestrated by a pair of glial cells that express UNC-6 (netrin). In the postsynaptic neuron RIA, the netrin receptor UNC-40 (DCC, deleted in colorectal cancer) plays a conventional guidance role, directing outgrowth of the RIA process ventrally toward the glia. In the presynaptic neuron AIY, UNC-40 (DCC) plays an unexpected and previously uncharacterized role: It cell-autonomously promotes assembly of presynaptic terminals in the immediate vicinity of the glial cell endfeet. These results indicate that netrin can be used both for guidance and local synaptogenesis and suggest that glial cells can function as guideposts during the assembly of neural circuits in vivo.
1 Department of Biological Sciences, Stanford University, 144 Herrin Laboratories, Stanford, CA 94305–5020, USA. 2 Neurosciences Program, Stanford University, Stanford, CA 94305–5020, USA.
* To whom correspondence should be addressed. E-mail: kangshen{at}stanford.edu
The editors suggest the following Related Resources on Science sites:
In Science Signaling
EDITORS' CHOICE
Pamela J. Hines (9 October 2007) Sci. STKE2007 (407), tw365.
[DOI: 10.1126/stke.4072007tw365] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Sumoylated MEF2A Coordinately Eliminates Orphan Presynaptic Sites and Promotes Maturation of Presynaptic Boutons.
T. Yamada, Y. Yang, J. Huang, G. Coppola, D. H. Geschwind, and A. Bonni (2013)
J. Neurosci.
33, 4726-4740
|Abstract »|Full Text »|PDF »
Serotonergic Neurosecretory Synapse Targeting Is Controlled by Netrin-Releasing Guidepost Neurons in Caenorhabditis elegans.
LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans.
P. Li, K. M. Collins, M. R. Koelle, and K. Shen (2013)
eLife Sci
2, e00378
|Abstract »|Full Text »|PDF »
Synaptic vesicle clustering requires a distinct MIG-10/Lamellipodin isoform and ABI-1 downstream from Netrin.
A. K. H. Stavoe, J. C. Nelson, L. A. Martinez-Velazquez, M. Klein, A. D. T. Samuel, and D. A. Colon-Ramos (2012)
Genes & Dev.
26, 2206-2221
|Abstract »|Full Text »|PDF »
Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton.
E. H. Najarro, L. Wong, M. Zhen, E. P. Carpio, A. Goncharov, G. Garriga, E. A. Lundquist, Y. Jin, and B. D. Ackley (2012)
J. Neurosci.
32, 4196-4211
|Abstract »|Full Text »|PDF »
A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development.
R. Christensen, L. de la Torre-Ubieta, A. Bonni, and D. A. Colon-Ramos (2011)
Development
138, 5257-5267
|Abstract »|Full Text »|PDF »
Different levels of the Tripartite motif protein, Anomalies in sensory axon patterning (Asap), regulate distinct axonal projections of Drosophila sensory neurons.
R. K. Morikawa, T. Kanamori, K.-i. Yasunaga, and K. Emoto (2011)
PNAS
108, 19389-19394
|Abstract »|Full Text »|PDF »
S6 kinase localizes to the presynaptic active zone and functions with PDK1 to control synapse development.
The Netrin Receptor DCC Is Required in the Pubertal Organization of Mesocortical Dopamine Circuitry.
C. Manitt, A. Mimee, C. Eng, M. Pokinko, T. Stroh, H. M. Cooper, B. Kolb, and C. Flores (2011)
J. Neurosci.
31, 8381-8394
|Abstract »|Full Text »|PDF »
Radial Glia: Progenitor, Pathway, and Partner.
M. Sild and E. S. Ruthazer (2011)
Neuroscientist
17, 288-302
|Abstract »|PDF »
Netrins: versatile extracellular cues with diverse functions.
K. L. W. Sun, J. P. Correia, and T. E. Kennedy (2011)
Development
138, 2153-2169
|Abstract »|Full Text »|PDF »
Genes Required for Cellular UNC-6/Netrin Localization in Caenorhabditis elegans.
T. Asakura, N. Waga, K.-i. Ogura, and Y. Goshima (2010)
Genetics
185, 573-585
|Abstract »|Full Text »|PDF »
Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance and nerve ring placement in C. elegans.
J. R. Kennerdell, R. D. Fetter, and C. I. Bargmann (2009)
Development
136, 3801-3810
|Abstract »|Full Text »|PDF »
Cell Adhesion, the Backbone of the Synapse: "Vertebrate" and "Invertebrate" Perspectives.
N. Giagtzoglou, C. V. Ly, and H. J. Bellen (2009)
Cold Spring Harb Perspect Biol
1, a003079
|Abstract »|Full Text »|PDF »
Control of CNS Synapse Development by {gamma}-Protocadherin-Mediated Astrocyte-Neuron Contact.
Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain.
C. Manitt, A. M. Nikolakopoulou, D. R. Almario, S. A. Nguyen, and S. Cohen-Cory (2009)
J. Neurosci.
29, 11065-11077
|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.