Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons

Sebastian Poliak, Daniel Morales, Louis-Philippe Croteau, Dayana Krawchuk, Elena Palmesino, Susan Morton, Jean-François Cloutier, Frederic Charron, Matthew B Dalva, Susan L Ackerman, Tzu-Jen Kao, Artur Kania

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
JournaleLife
Volume4
DOIs
Publication statusPublished - 2015

Fingerprint

Ephrins
Motor Neurons
Neurons
Axons
Growth Cones
Cones
Ephrin-B2
Trajectories
Eph Family Receptors
src-Family Kinases
Cues
Assays
Extremities
Ligands
Networks (circuits)
Population
Axon Guidance
netrin-1
netrin receptors

Keywords

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Poliak, S., Morales, D., Croteau, L-P., Krawchuk, D., Palmesino, E., Morton, S., ... Kania, A. (2015). Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons. eLife, 4. https://doi.org/10.7554/eLife.10841

Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons. / Poliak, Sebastian; Morales, Daniel; Croteau, Louis-Philippe; Krawchuk, Dayana; Palmesino, Elena; Morton, Susan; Cloutier, Jean-François; Charron, Frederic; Dalva, Matthew B; Ackerman, Susan L; Kao, Tzu-Jen; Kania, Artur.

In: eLife, Vol. 4, 2015.

Research output: Contribution to journalArticle

Poliak, S, Morales, D, Croteau, L-P, Krawchuk, D, Palmesino, E, Morton, S, Cloutier, J-F, Charron, F, Dalva, MB, Ackerman, SL, Kao, T-J & Kania, A 2015, 'Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons', eLife, vol. 4. https://doi.org/10.7554/eLife.10841
Poliak S, Morales D, Croteau L-P, Krawchuk D, Palmesino E, Morton S et al. Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons. eLife. 2015;4. https://doi.org/10.7554/eLife.10841
Poliak, Sebastian ; Morales, Daniel ; Croteau, Louis-Philippe ; Krawchuk, Dayana ; Palmesino, Elena ; Morton, Susan ; Cloutier, Jean-François ; Charron, Frederic ; Dalva, Matthew B ; Ackerman, Susan L ; Kao, Tzu-Jen ; Kania, Artur. / Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons. In: eLife. 2015 ; Vol. 4.
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