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Publication : Celsr3 is required in motor neurons to steer their axons in the hindlimb.

First Author  Chai G Year  2014
Journal  Nat Neurosci Volume  17
Issue  9 Pages  1171-9
PubMed ID  25108913 Mgi Jnum  J:215832
Mgi Id  MGI:5607185 Doi  10.1038/nn.3784
Citation  Chai G, et al. (2014) Celsr3 is required in motor neurons to steer their axons in the hindlimb. Nat Neurosci 17(9):1171-9
abstractText  The cadherin Celsr3 regulates the directional growth and targeting of axons in the CNS, but whether it acts in collaboration with or in parallel to other guidance cues is unknown. Furthermore, the function of Celsr3 in the peripheral nervous system is still largely unexplored. Here we show that Celsr3 mediates pathfinding of motor axons innervating the hindlimb. In mice, Celsr3-deficient axons of the peroneal nerve segregate from those of the tibial nerve but fail to extend dorsally, and they stall near the branch point. Mutant axons respond to repulsive ephrinA-EphA forward signaling and glial cell-derived neurotrophic factor (GDNF). However, they are insensitive to attractive EphA-ephrinA reverse signaling. In transfected cells, Celsr3 immunoprecipitates with ephrinA2, ephrinA5, Ret, GDNF family receptor alpha1 (GFRalpha1) and Frizzled3 (Fzd3). The function of Celsr3 is Fzd3 dependent but Vangl2 independent. Our results provide evidence that the Celsr3-Fzd3 pathway interacts with EphA-ephrinA reverse signaling to guide motor axons in the hindlimb.
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