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Publication : Lysosomal dynamics regulate mammalian cortical neurogenesis.

First Author  Zou W Year  2024
Journal  Dev Cell Volume  59
Issue  1 Pages  64-78.e5
PubMed ID  38103552 Mgi Jnum  J:344234
Mgi Id  MGI:7574076 Doi  10.1016/j.devcel.2023.11.021
Citation  Zou W, et al. (2024) Lysosomal dynamics regulate mammalian cortical neurogenesis. Dev Cell 59(1):64-78.e5
abstractText  Mammalian neocortex formation follows a stereotypical pattern wherein the self-renew and differentiation of neural stem cells are coordinated with diverse organelle dynamics. However, the role of lysosomes in brain development has long been overlooked. Here, we demonstrate the highly dynamic lysosomal quantities, types, and localizations in developing brain. We observed asymmetric endolysosome inheritance during radial glial cell (RGC) division and the increased autolysosomes within intermediate progenitor cells (IPs) and newborn neurons. Disruption of lysosomal function shortens the S phase of the cell cycle and promotes RGC differentiation. Mechanistically, we revealed a post-transcriptional regulation governing ribosome homeostasis and cell-cycle progression through differential lysosomal activity modulation. In the human forebrain organoid, lysosomal dynamics are conserved; specifically, during the mitosis of outer subventricular zone RGCs (oRGs), lysosomes are inherited by the progeny without basal process. Together, our results identify the critical role of lysosomal dynamics in regulating mouse and human brain development.
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