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Lysosomal dynamics regulate mammalian cortical neurogenesis.

Wenzheng Zou1, Yuqing Lv2, Shukui Zhang2

  • 1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Affiliated Hospital of Guangdong Medical University & Key Laboratory of Zebrafish Model for Development and Disease of Guangdong Medical University, Zhanjiang 523710, China.

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|December 16, 2023
PubMed
Summary

Lysosomes play a dynamic role in brain development, influencing neural stem cell division and differentiation. This study reveals their critical function in mammalian neocortex formation.

Keywords:
asymmetric cell divisioncell-cycle progressionhuman brain organoidlysosomal dynamicsneural stem cellneurogenesisouter subventricular zone radial glial cellpost-transcriptional regulation

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Mammalian neocortex development involves coordinated neural stem cell self-renewal and differentiation with organelle dynamics.
  • The specific role of lysosomes in brain development has been largely unexplored.

Purpose of the Study:

  • To investigate the dynamic nature and function of lysosomes during mammalian brain development.
  • To elucidate the mechanisms by which lysosomal activity influences neural stem cell behavior and cell-cycle progression.

Main Methods:

  • Observation of lysosomal quantities, types, and localization in developing mouse brains.
  • Analysis of lysosomal inheritance patterns during radial glial cell (RGC) division.
  • Assessment of the effects of lysosomal function disruption on cell-cycle phases and RGC differentiation.
  • Investigation using human forebrain organoids to confirm conserved lysosomal dynamics.

Main Results:

  • Lysosomal dynamics, including asymmetric inheritance and autolysosome increase, are prominent in developing brains.
  • Disrupting lysosomal function accelerates the cell cycle's S phase and promotes RGC differentiation.
  • Lysosomal activity modulates ribosome homeostasis and cell-cycle progression via post-transcriptional regulation.
  • Conserved lysosomal inheritance patterns were observed in human forebrain organoids during outer RGC mitosis.

Conclusions:

  • Lysosomal dynamics are critical and conserved regulators of mammalian (mouse and human) brain development.
  • Lysosomes actively participate in coordinating neural stem cell fate decisions and cell-cycle control.
  • This research highlights lysosomes as key players in neocortex formation, opening new avenues for understanding neurodevelopmental processes.