Commissural axons of the spinal cord are a widely used model to study molecular mechanisms of axon guidance.After crossing the floor plate, the ventral midline of the spinal cord, axons of dorsolateral commissural neurons turn into the longitudinal axis and extend in rostral direction.A variety of cues have been identified for guidance towards and across the midline.The morphogen Sonic hedgehog (Shh) was identified as a chemoattractant for commissural axons that acts in parallel to Netrin (Charron et al., Cell 2003).After reaching the midline, commissural axons change their responsiveness to Shh by switching receptors.Hedgehog-interacting protein (Hhip) mediates a repulsive activity of Shh guiding post-crossing commissural axons rostrally, in accordance with the anterolow-posteriorhigh gradient of Shh in the floor plate (Bourikas et al., Nat.Neurosci.2005).In the mouse, Wnt4 expressed in an anterohigh-posteriorlow gradient was shown to attract post-crossing commissural axons rostrally (Lyuksyutova et al., Science 2003).We found that Wnts also act as axon guidance cues in the chicken spinal cord.However, in contrast to the mouse, Wnt transcription did not differ along the anteroposterior axis of the chicken spinal cord (Domanitskaya et al., J.Neurosci.2010).Rather, Wnt activity was regulated by a graded distribution of Sfrps (Secreted frizzled-related proteins) that in turn appears to be shaped by the graded expression of Shh.Thus, Shh affects post-crossing eommissural axon guidance both directly and indirectly by regulating Wnt activity.