摘要:SummaryGangliosides are present and concentrated in axons and implicated in axon-myelin interactions, but how ganglioside composition changes during myelin formation is not known. Here, we present a direct infusion (shotgun) lipidomics method to analyze gangliosides in small amounts of tissue reproducibly and with high sensitivity. We resolve the mouse ganglioside lipidome during development and adulthood and determine the ganglioside content of mice lacking theSt3gal5andB4galnt1genes that synthesize most ganglioside species. Our results reveal substantial changes in the ganglioside lipidome during the formation of myelinated nerve fibers. In sum, we provide insights into the CNS ganglioside lipidome with a quantitative and sensitive mass spectrometry method. Since this method is compatible with global lipidomic profiling, it will provide insights into ganglioside function in physiology and pathology.Graphical abstractDisplay OmittedHighlights•A sensitive direct infusion mass spectrometry method for ganglioside lipidomics•Quantification of gangliosides in CNS myelin development•Generation of myelin in the absence of gangliosidesNeuroscience; Cell biology; Omics.