Regulation of neuronal polarity

•Neuronal polarization relies on coordinated actin/microtubule dynamics.•Directed membrane traffic and local protein degradation are also crucial.•Regulated PI3K and small GTPase signaling ensure axon initiation.•The PAR complex, LKB1 and SAD kinases are key regulators of neuronal polarity.•Complex signaling regulates distinct modes of neuronal polarization in vivo

The distinctive polarized morphology of neuronal cells is essential for the proper wiring of the nervous system. The rodent hippocampal neuron culture established about three decades ago has provided an amenable in vitro system to uncover the molecular mechanisms underlying neuronal polarization, a process relying on highly regulated cytoskeletal dynamics, membrane traffic and localized protein degradation. More recent research in vivo has highlighted the importance of the extracellular environment and cell–cell interactions in neuronal polarity. Here, I will review some key signaling pathways regulating neuronal polarization and provide some insights on the complexity of this process gained from in vivo studies.