Molecular Mechanisms Underlying Pluripotency and Lineage Commitment – The Role of GSK-3

The highly related serine/threonine kinases GSK3┙ and GSK3┚ are transducers of Wnt/┚catenin, PI-3K, Notch and Hedgehog signalling pathways, placing them at the hub of key developmental and metabolic processes. There is accumulating evidence suggesting that GSK-3 inhibitors aid in the acquisition or sustenance of pluripotency in embryonic stem cells of mouse, rat and human origin. However, the mechanism through which GSK-3 inhibitors impart their effects is unclear due to the myriad cellular processes in which GSK-3 plays a role. Here, we review the studies that have examined the consequences of GSK-3 inhibition in pluripotent stem cells with a focus on key signalling pathways, which have been implicated in GSK-3 inhibitor-mediated effects.