A Spatio-Temporal Sequence of Axonal Sensitization to Slits and Semaphorins Orchestrates Commissural Axon Navigation
40 Pages Posted: 8 Apr 2019 Sneak Peek Status: Under ReviewMore...
Accurate perception of guidance cues is crucial for cell and axon migration. During initial navigation in the spinal cord, commissural axons are kept insensitive to midline repellents. Upon midline crossing in the floor plate, they switch on responsiveness to Slit and Semaphorin repulsive signals and are propelled away and prevented from crossing back. Whether and if so how the different midline repellents control specific aspects of the navigation remain puzzling. We set-up a paradigm for live imaging and super resolution analysis of PlexinA1, Neuropilin- 2 and Robo1/2 receptor dynamics during commissural growth cone navigation in chick and mouse embryos. We uncovered a remarkable program of sensitization to midline cues achieved by unique spatio-temporal sequences of receptor allocation at the growth cone surface, eliciting receptor-specific growth cone behavior changes. This reveals post-translational mechanisms whereby coincident guidance signals are temporally resolved, which thus allow the generation of peculiar guidance responses.
Keywords: axon guidance, guidance receptors, Roundabout1/2, PlexinA1, Neuropilin2, spinal cord commissure, midline spinal cord commissure, FRAP live imaging
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