Lipids as new players in axon guidance and circuit development

The formation of functional neuronal circuitry depends on axon guidance, in which extracellular chemotropic cues provide directional instructions to developing axons in the embryonic nervous system. Recently lipids, in particular lysolipids, are being appraised as a new class of axon guidance cues. Most lysolipids are formed by enzymatic hydrolysis of membrane phospholipids, and signal via a wide variety of mechanisms including specific G protein-coupled receptors. For example, lysophosphatidylglucoside released from a specific type of glia activates neuronal GPR55 to regulate axon tract patterning. However, demonstrating the in vivo mechanisms of lysolipid axon guidance is often challenging and complex. Here we will review in detail lysolipids that have been identified or proposed as axon guidance cues in the developing nervous system.