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First published online September 12, 2006
doi: 10.1242/10.1242/dev.02564
1 SORST, Japan Science and Technology, Japan.
2 Graduate School of Frontier Biosciences, Osaka University, Yamadaoka 1-3,
Suita, Osaka 565-0871, Japan.
3 MRC Centre for Developmental Neurobiology, King's College London, Guy's
Campus, London SE1 1UL, UK.
* Authors for correspondence (e-mail: yan.zhu{at}fbs.osaka-u.ac.jp; murakami{at}fbs.osaka-u.ac.jp)
Accepted 3 August 2006
Most post-crossing commissural axons turn into longitudinal paths to make synaptic connections with their targets. Mechanisms that control their rostrocaudal turning polarity are still poorly understood. We used the hindbrain as a model system to investigate the rostral turning of a laterally located commissural tract, identified as the caudal group of contralateral cerebellar-projecting second-order vestibular neurons (cC-VC). We found that the caudal hindbrain possessed a graded non-permissive/repulsive activity for growing cC-VC axons. This non-permissiveness/repulsion was in part mediated by glycosyl-phosphatidylinositol (GPI)-anchored ephrin A. We further demonstrated that ephrin A2 was distributed in a caudal-high/rostral-low gradient in the caudolateral hindbrain and cC-VC axons expressed EphA receptors. Finally, perturbing ephrin A/EphA signalling both in vitro and in vivo led to rostrocaudal pathfinding errors of post-crossing cC-VC axons. These results suggest that ephrin A/EphA interactions play a key role in regulating the polarity of post-crossing cC-VC axons as they turn into the longitudinal axis.
Key words: Commissural axons, Ephrin A, Longitudinal polarity, Hindbrain, Chick