| Abstract No.: | C-A3003 |
| Country: | Canada |
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| Title: | NETRIN SIGNALING COORDINATES THE TOPOGRAPHY OF SPINAL MOTOR NEURON AXON PROJECTIONS |
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| Authors/Affiliations: | 1 Dayana Krawchuk*; 1,2 Frédéric Charron; 2 Artur Kania;
1Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins, Montréal, QC, Canada
2Division of Experimental Medicine and Department of Anatomy and Cell
Biology, McGill University, Montréal, QC, Canada; Faculté de Médecine,
Université de Montréal, QC, Canada.
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| Content: | Objectives: Precise connections between neurons and their targets are specified using a limited complement of axon guidance molecules. To understand this process, we study the selection of axon trajectory by lateral motor column (LMC) spinal motor axons at the base of the limb. Lateral LMC axons select a dorsal limb trajectory, whereas medial LMC neurons select a ventral limb trajectory. These choices are controlled, in part, by ephrin:Eph short-range signaling, however, genetic evidence suggests the existence additional axon guidance cues. To uncover these, we screened for molecules whose expression is restricted to the dorsal or ventral limb mesenchyme, and found that Netrin1, a diffusible molecule required for long-range attractive or repulsive guidance of many classes of axons, was expressed in the dorsal limb near the entry point of LMC axons.
Methods: To test the idea that Netrin1 is a bifunctional axon guidance cue that attracts lateral LMC axons to the dorsal limb and repels medial LMC axons towards the ventral limb, we determined the mRNA expression profile of its receptors and retrogradely labeled LMC projections in embryos mutant for genes encoding Netrin1 signaling pathway components.
Results: We find that receptors mediating Netrin1 attraction are expressed by lateral LMC motor neurons while receptors associated with Netrin1 repulsion are expressed by medial LMC motor neurons. Our retrograde LMC axon projection tracing from dorsal or ventral musculature in mice mutant for Netrin1 or genes encoding its receptors demonstrates that loss of Netrin1 signaling leads to significant LMC axon pathfinding errors in the limb.
Conclusions: Our observations are consistent with Netrin1 acting as a bifunctional axon guidance cue attractive to lateral LMC axons and repulsive to medial LMC axons, suggesting that both long- and short-range guidance cues control LMC axon pathfinding.
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