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Esther Stoeckli"Morphogens collaborate with classical axon guidance cues to direct post-crossing commissural axons into the longitudinal axis of the spinal cord"

Abstract :

Morphogens collaborate with classical axon guidance cues to direct post-crossing commissural axons into the longitudinal axis of the spinal cord .

Commissural axons in 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., 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 postcommissural axons rostrally, in accordance with the anterolow-posteriorhigh gradient of Shh in the floor plate (Bourikas et al., 2005).

In the mouse, Wnt4 expressed in an anterohigh-posteriorlow gradient was shown to attract postcommissural axons rostrally (Lyuksyutova et al., 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. 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 postcommissural axon guidance both directly and indirectly by regulating Wnt activity.
In addition to morphogens also 'classical' axon guidance cues, such as cell adhesion molecules of the immunoglobulin superfamily are involved in guidance of post-crossing commissural axons. In particular, we found a role for the synaptic cell adhesion molecules SynCAM/Nectin-like molecules in post-crossing commissural axon guidance (Niederkofler et al., 2010).

Selected publications

Domanitskaya E, Wacker A, Mauti O, Baeriswyl T, Esteve P, Bovolenta P, Stoeckli ET (2010) Sonic hedgehog guides post-crossing commissural axons both directly and indirectly by regulating Wnt activity. J Neurosci 30:11167-11176.
Holz A, Kollmus H, Ryge J, Niederkofler V, Dias J, Ericson J, Stoeckli ET, Kiehn O, Arnold HH (2010) The transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor-plate development and commissural axon guidance. Development, 137:4249-4260
Niederkofler V, Baeriswyl T, Ott R, Stoeckli ET (2010) Nectin-like molecules/SynCAMs are required for post-crossing commissural axon guidance. Development 137:427-435.
Petrinovic MM, Duncan CS, Bourikas D, Weinman O, Montani L, Schroeter A, Maerki D, Sommer L, Stoeckli ET, Schwab ME (2010) Neuronal Nogo-A regulates neurite fasciculation, branching and extension in the developing nervous system. Development 137:2539

Stoeckli ET (2010) Neural circuit formation in the cerebellum is controlled by cell adhesion molecules of the contactin family. Cell Adh Migr 4: 523-52

Nathalie Sans