Figure 1. A Schematic Illustration of The role of Oxysterols in Promoting Dopaminergic Neurogenesis.

Dopaminergic neural progenitors undergo active cell-cycle progression in the ventral midbrain domain from the mouse embryonic stage E9 to E12 and then dopaminergic neuron fate determination and maturation from the stage E11 to E15 (A). Acting in the nuclei of the early progenitors in a presumably cell-autonomous manner, oxysterols (22-oxycholesterol depicted) activate LXRs and regulate target gene transcription to induce cell-cycle exit and dopamine neuron differentiation. Such effects of oxysterols are conserved during dopaminergic neurogenesis from human embryonic stem cells (B). Shh and Fgf8 induce neural progenitor cell competency for midbrain neuron specification. By inducing cell-cycle exit specifically toward neuronal fate, oxysterols then act in coordination with other factors and genetic programs to promote dopaminergic neuron differentiation from progenitor cells.