Long and Short-Term Effect of mTOR Regulation on Cerebral Organoid Growth and Differentiations

The mammalian target of rapamycin (mTOR) signaling is critical for the maintenance and differentiation of neurogenesis, and conceivably for many other brain developmental processes. However, in vivo studies of mTOR functions in the brain are often hampered due to the essential role of the associated signaling in brain development. We monitored the long- and short-term effects of mTOR signaling regulation on cerebral organoids growth, differentiation and function using an mTOR inhibitor (everolimus) and an mTOR activator (MHY1485). Short-term treatment with MHY1485 induced faster organoid growth and differentiation, while long-term treatment induced the maturation of cerebral organoids. These data suggest that the optimal activity of mTOR is crucial in maintaining normal brain development, and its role is not confined to the early neurogenic phase of brain development.