Neurons are highly compartmentalised cells, with axonal and dendritic compartments distinct from the cell body (soma). It is now recognised that local regulation of protein synthesis in these different compartments is important for neuronal development and function. Now, Federico Dajas-Bailador and colleagues demonstrate a local axonal role for the micro-RNA miR-26a in mouse primary cortical neurons to regulate both axon development and growth. Inhibition of miR-26a leads to reduced axon length and defects in neuronal polarisation, while overexpression of a miR-26a mimic promotes axon growth and induces a multiple axon phenotype. These effects are mediated at least partly via translational regulation of GSK3β, a known miR-26a target and regulator of neuronal polarity and axon growth. Using a compartmentalised microfluidic culture system, the authors show that localised miR-26a represses GSK3β translation in the axonal compartment. Upon inhibition of miR-26a activity, GSK3β can be synthesised locally in the axon and transported back to the soma – this translocation is required for GSK3β function in axon growth. Together, these data demonstrate how a single miRNA can regulate protein translation of GSK3β in the axon, controlling cellular communication to the soma in a process that influences neuronal development.
