Celsr3 is required in motor neurons to steer their axons in the hindlimb
(2014) Nature Neuroscience — Vol. 17, n° 9, p. 1171-1179 (2014)
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- Authors
Tissir, Fadel 
- Abstract
- Celsr3 regulates the directional growth and targeting of axons in the central nervous system (CNS), but whether it acts in collaboration with or in parallel to other guidance cues is unknown. Furthermore, the role of Celsr3 in the peripheral nervous system (PNS) is still largely unexplored. Here, we show that Celsr3 plays a key role in pathfinding of motor axons innervating the hindlimb. Celsr3–deficient axons of the peroneal nerve segregate from those of the tibial nerve, but fail to extend dorsally and stall near the branching point. Mutant axons respond to repulsive ephrinA:EphA forward signaling and GDNF. However, they are insensitive to attractive EphA:ephrinA reverse signaling. In transfected cells, Celsr3 co-immunoprecipitates with ephrinA2/A5, Ret, GFRαand Fzd3. The function of Celsr3 is Fzd3-dependent but Vangl2-independent. Our results provide evidence that Celsr3/Fzd3 interacts with EphA:ephrinA reverse signaling to guide motor axons in the hindlimb.
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Citations
Chai, G., Zhou, L., Manto, M., Helmbacher, F., Clotman, F., Goffinet, A., & Tissir, F. (2014). Celsr3 is required in motor neurons to steer their axons in the hindlimb. Nature Neuroscience, 17(9), 1171-1179. https://doi.org/10.1038/nn.3784 (Original work published 2014)