Figure 2.

Model of miRNA-mediated regulation of axon guidance. During pathfinding, tight regulation of mRNAs occurs to ensure protein expression of guidance molecules at the right time and place, and enable accurate growth cone steering. Within projection neurons, transcripts are translated into the cell body and are subsequently transported within the axon to the growth cone to mediate guidance cue-induced signaling. Alternatively, mRNAs associate into messenger ribonucleoprotein particles (mRNPs) to be transported to the growth cone, where they can be locally translated. Retrograde transport of transcripts from growth cones to cell soma also exists (not represented here). miRNAs are speculated to act at multiple level. They may regulate transcripts translation and stability (1) within the cell body as suggested for miR-124 and lin-4 (Baudet et al., 2012; Zhang et al., 2013) or (2) directly within growth cones as suggested for miR-134 (Han et al., 2011) and by the presence of RISC within this compartment (Table 3). (3) As speculated (Kosik, 2006), miRNAs may translocate along the axons alone or within mRNPs (shown here) and/or be transported as pre-miRNAs and locally produced within growth cones. Guidepost cells are important partners for projection neurons, as they provide them with positional information through the expression of guidance cues. The regulation of guidepost cell transcriptome is thus of crucial importance to ensure the correct patterning of these cells and also the delivery of the right guidance cue at the right place. miRNAs could act by directly regulating the expression of guidance cues within guidepost cells (4) or by indirectly regulating molecules involved in the patterning of these cells (5), as suggested for miR-9 (Shibata et al., 2011).