This message will self-destruct: NMD regulates axon guidance

Abstract

The navigation of axons to their final destination can involve a sequence of steps that require different sets of guidance receptors. In this issue, Colak et al. show that regulated intra-axonal protein synthesis coupled to nonsense-mediated mRNA decay (NMD) controls a switch in Robo3.2 expression that is critical for navigation.

Figure 1. NMD in commissural axon guidance

(A) Guidance of commissural axons across the midline floor plate involves a switch from attraction to repulsion. Robo3.2 is upregulated upon crossing. (B) Robo3.2 is a repellent receptor for the midline cue Slit. In NMD-deficient Upf2 knockout neurons, Robo3.2 level is increased, and axon trajectories are further from the midline. (C) Model for midline activation of mRNA translation coupled to NMD. The NMD pathway inhibits further translation and promotes mRNA degradation.