Regulation of sphingolipid metabolism in neurogenesis

Several studies have established the importance of sphingolipids in brain development. Defects in sphingolipid synthesis indeed cause gross brain abnormalities, demyelination, seizures, and paraplegia in mammals. Moreover, food contaminations with the mycotoxin and sphingolipid synthesis inhibitor Fumonisin B1 cause neural tube closure defects in newborns. During neuronal differentiation Embryonic Stem Cells (ESC) remodel their sphingolipid profile from expressing globosides to expressing gangliosides in neurons. This transition depends on a switch in the expression of the genes encoding the relevant glycosphingolipid synthesizing enzymes. Recently, we have shown that this globo to ganglio switch is internally regulated and triggered by reduction in cellular globo-series glycosphingolipid content. In this line of research, we aim at identifying the factors that initiate and assist the sphingolipid metabolic reprogramming during neural differentiation and to understand the basis of neural diseases deriving from impaired sphingolipid metabolism.