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

Sung Bum Park1, Byungho Lim1, Ki Young Kim2

  • 1Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea.

Tissue Engineering and Regenerative Medicine
|December 28, 2023
PubMed
Abstract

Insights

Optimal mammalian target of rapamycin (mTOR) signaling is vital for brain development beyond early neurogenesis. Studies on cerebral organoids show mTOR regulation impacts growth, differentiation, and maturation.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Signaling

Background:

  • Mammalian target of rapamycin (mTOR) signaling is crucial for neurogenesis and brain development.
  • In vivo studies on mTOR's role in brain development are challenging due to its essential functions.

Purpose of the Study:

  • To investigate the long- and short-term effects of mTOR signaling modulation on cerebral organoid development.
  • To understand the broader role of mTOR in brain development beyond the initial neurogenic phase.

Main Methods:

  • Utilized cerebral organoids as a model system.
  • Applied an mTOR inhibitor (everolimus) and an mTOR activator (MHY1485) to modulate signaling pathways.
  • Monitored organoid growth, differentiation, and function over time.

Main Results:

  • Short-term activation of mTOR signaling (MHY1485) accelerated organoid growth and differentiation.
  • Long-term activation of mTOR signaling promoted the maturation of cerebral organoids.
  • Modulation of mTOR signaling impacts multiple stages of brain development in vitro.

Conclusions:

  • Optimal mTOR activity is essential for normal brain development.
  • The function of mTOR in brain development extends beyond the early neurogenic period.
  • Cerebral organoids are a valuable tool for studying complex developmental processes and signaling pathways.
Keywords:
Cerebral organoidsDifferentiationGrowthmTOR regulation

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