Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons
- Columbia University, United States
- Institut de recherches cliniques de Montreal, Canada
- Montreal Neurological Institute, Canada
- Department of Neuroscience, The Farber Institute for Neurosciences, Jefferson Hospital for Neuroscience, United States
- Howard Hughes Medical Institute, The Jackson Laboratory, United States
- Taipei Medical University, Taiwan
Abstract
During neural circuit assembly, axonal growth cones are exposed to multiple guidance signals at trajectory choice points. While axonal responses to individual guidance cues have been extensively studied, less is known about responses to combination of signals and underlying molecular mechanisms. Here, we studied the convergence of signals directing trajectory selection of spinal motor axons entering the limb. We first demonstrate that Netrin-1 attracts and repels distinct motor axon populations, according to their expression of Netrin receptors. Quantitative in vitro assays demonstrate that motor axons synergistically integrate both, attractive or repulsive Netrin-1 signals together with repulsive ephrin signals. Our investigations of the mechanism of ephrin-B2 and Netrin-1 integration demonstrate that the Netrin receptor Unc5c and the ephrin receptor EphB2 can form a complex in a ligand-dependent manner and that Netrin-ephrin synergistic growth cones responses involve the potentiation of Src family kinase signaling, a common effector of both pathways.
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Ethics
Animal experimentation: All experimental procedures were approved by the Animal Care Committee at the Institut de Recherches Cliniques de Montréal, in accordance with the regulations of the Canadian Council on Animal Care. The following protocol reference numbers were used: 2005-03, 2008-18, 2009-10, 2011-30 and 2012-22.
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© 2015, Poliak et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons
eLife 4:e10841.
https://doi.org/10.7554/eLife.10841
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