Diffusible molecules of the Slit family inhibit midline crossing by axons and neurons that express Robo receptors. For example, migrating inferior olive (IO) neurons extend a leading process across the midline, but the somata stop upon reaching the floor plate, which expresses Slits; the leading process forms the axon. Robo3 knock-out prevents midline crossing by the leading process, suggesting that Robo3 may interfere with repulsive signaling by other Slit–Robo pairs. To test this hypothesis, Di Meglio et al. knocked out Slits and Robos individually and in combination. As expected, IO somata crossed the midline in Slit1/2 and Robo1/2 knock-outs, confirming that these proteins normally repel neurons. Unexpectedly, however, axons failed to cross the midline in Robo1/2/3 triple knock-outs, indicating that Robo3 actively promotes crossing, rather than simply interfering with Robo1/2 signaling. In addition, the patterning of IO subnuclei was disrupted in knock-outs, suggesting an additional role for Slits and Robos.
Robos and Slits in Inferior Olive Development
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