miR-92 Suppresses Robo1 Translation to Modulate Slit Sensitivity in Commissural Axon Guidance

Temporospatial regulation of guidance signaling is essential for axon outgrowth and pathfinding in the developing nervous system. Regulation of Robo1 levels in commissural neurons modulates Slit sensitivity facilitating proper axon guidance. The mechanisms underlying this regulation in the vertebrate nervous system are not well understood. Here, we report that miR-92, a highly conserved microRNA (miRNA), regulates chicken Robo1 expression in commissural neurons by binding to the 3' untranslated region (3' UTR) of Robo1 mRNA. miR-92 and Robo1 are differentially expressed in the developing spinal cord. miR-92 interacts with the Robo1 3'UTR to cause translational repression, but not mRNA degradation. Disruption of the miR-92/Robo1 3' UTR interaction induces premature responsiveness to Slit2 repulsion of precrossing commissural axons (CAs) in vitro and causes CA projection defects in vivo. These results indicate that miR-92 represses Robo1 expression thereby regulating Slit sensitivity to control CA projection and midline crossing.