Researchers have made a surprising discovery linking Delta/Notch signaling in subperineurial glia (SPG) to the regulation of nerve ensheathment and neurotransmitter release at the Drosophila neuromuscular junction (NMJ). SPG, the counterpart of the endothelial layer in the vertebrate blood-brain barrier, form the key cellular layer that is critical for axonal ensheathment and the blood-brain barrier in Drosophila. The results provide a mechanistic insight into the biology of barrier function and glia-neuron interactions.