Fig. 2.

Specific gangliosides modulate NSC function and neuronal differentiation. Our published data suggest that GD3 maintains NSC’s characteristics and GM1 epigenetically promotes neuronal differentiation of NSCs. ST-II (GD3S) and GalNAcT (GM2/GD2S) are located at a key branching point of a- and b-series ganglioside biosynthetic pathways (Fig. 1). GD3 modulates NSC proliferation by interacting with growth factor receptors and regulating growth factor-induced signaling. The synthesis of GD3 is switched into the synthesis of complex gangliosides (GM1, GD1a, GD1b, and GT1b), resulting in terminal differentiation and loss of the “stemness” of NSCs. During neuronal differentiation, the expression of complex a-series gangliosides, especially GM1, is augmented by a GM1-modulated epigenetic gene regulation mechanism of GalNAcT. Nuclear GM1 modulates transcriptional activity of neuronal genes, such as Neuro D1. NSC, neural stem cell; NPC, neuronal progenitor cell