Mechanisms of synaptic pruning in the developing brain
Neuron–microglial communication is mediated by both the formation of new synapses and the selective removal of unnecessary connections through synaptic pruning. Recent findings suggest that superfluous connections are eliminated by microglia, and 70 % of the connections in a primate cortex are lost within six months of life. Several eat-me signals in synaptic pruning have been identified, but spare-me signals limiting phagocytic elimination have not been established. Sialic acid in neuronal glycocalyx acts as a spare-me signal and prevents microglial phagocytosis through Siglec receptors, and aberrant regulation of sialic acid causes neuronal loss and embryonic lethality. The EU-funded SinGly project aims to investigate whether sialidases, glycocalyx recognising proteins, are developmentally regulated and study the role of sialic acid in synaptic pruning during neurodevelopment.