Lysosomal dynamics regulate mammalian cortical neurogenesis.
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.
Pubmed ID: 38103552 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
None foundAntibodies used in this publication
- TFEB Rabbit pAb (RRID:AB_3065229)
- HA-Tag (C29F4) Rabbit mAb (RRID:AB_1549585)
- mTOR (7C10) Rabbit mAb (RRID:AB_2105622)
- CD107a (LAMP-1) (RRID:AB_2134499)
- Mouse Anti-Human NeuroD1 Monoclonal Antibody, Unconjugated (RRID:AB_943491)
- EIF4E Antibody, RIP-grade (RRID:AB_1570634)
- Phospho-mTOR (Ser2448) (D9C2) XP Rabbit mAb (RRID:AB_10691552)
- Beta Actin antibody (RRID:AB_10700003)
- [KO Validated] LC3B Rabbit mAb (RRID:AB_2862723)
- Recombinant Anti-SQSTM1 / p62 antibody [EPR4844] - Autophagosome Marker (RRID:AB_2810880)
- LAMP1 (D4O1S) Mouse mAb (RRID:AB_2798750)
- LAMP1 (D2D11) XP Rabbit Antibody (RRID:AB_2687579)
- Prealbumin/transthyretin antibody (RRID:AB_2212083)
- HOPX antibody (RRID:AB_10693525)
- Phospho-Vimentin (Ser82) (RRID:AB_592969)
- Anti-4E-BP1, phospho (Thr37 / Thr46) Monoclonal Antibody (RRID:AB_560835)
- Rat Anti-BrdU Monoclonal Antibody, Unconjugated, Clone BU1 / 75 (ICR1) (RRID:AB_305426)
- Rabbit Anti-Histone H3, phospho (Ser10) Monoclonal Antibody, Unconjugated, Clone D2C8 (RRID:AB_1549592)
- NeuroD2 antibody (RRID:AB_10975628)
- EOMES Monoclonal Antibody (Dan11mag), eBioscience (RRID:AB_11042577)
- Rabbit Anti-Mouse TBR2 / Eomes Polyclonal Antibody, Unconjugated (RRID:AB_778267)
- Rabbit Anti-PAX6 , Unconjugated (RRID:AB_1587367)
- Human/Mouse/Rat SOX2 Antibody (RRID:AB_355110)
- Sox2 (C70B1) Rabbit mAb (IHC Preferred) (RRID:AB_2194037)
Associated grants
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This is a list of tools and resources that we have found mentioned in this publication.
TFEB Rabbit pAb (antibody)
RRID:AB_3065229
This polyclonal targets TFEB
View all literature mentionsHA-Tag (C29F4) Rabbit mAb (antibody)
RRID:AB_1549585
This monoclonal targets HA-Tag
View all literature mentionsmTOR (7C10) Rabbit mAb (antibody)
RRID:AB_2105622
This monoclonal targets mTOR
View all literature mentionsCD107a (LAMP-1) (antibody)
RRID:AB_2134499
This monoclonal targets Lamp1
View all literature mentionsMouse Anti-Human NeuroD1 Monoclonal Antibody, Unconjugated (antibody)
RRID:AB_943491
This monoclonal targets Human NeuroD1
View all literature mentionsEIF4E Antibody, RIP-grade (antibody)
RRID:AB_1570634
This polyclonal targets Human EIF4E
View all literature mentionsPhospho-mTOR (Ser2448) (D9C2) XP Rabbit mAb (antibody)
RRID:AB_10691552
This monoclonal targets Phospho-mTOR (Ser2448)
View all literature mentionsBeta Actin antibody (antibody)
RRID:AB_10700003
This polyclonal targets Beta Actin
View all literature mentions[KO Validated] LC3B Rabbit mAb (antibody)
RRID:AB_2862723
This monoclonal targets
View all literature mentionsRecombinant Anti-SQSTM1 / p62 antibody [EPR4844] - Autophagosome Marker (antibody)
RRID:AB_2810880
This recombinant targets SQSTM1 / p62
View all literature mentionsLAMP1 (D4O1S) Mouse mAb (antibody)
RRID:AB_2798750
This monoclonal targets LAMP1
View all literature mentionsLAMP1 (D2D11) XP Rabbit Antibody (antibody)
RRID:AB_2687579
This monoclonal targets LAMP1
View all literature mentionsPrealbumin/transthyretin antibody (antibody)
RRID:AB_2212083
This polyclonal targets Prealbumin/transthyretin
View all literature mentionsPhospho-Vimentin (Ser82) (antibody)
RRID:AB_592969
This monoclonal targets Vimentin, phospho (Ser82)
View all literature mentionsAnti-4E-BP1, phospho (Thr37 / Thr46) Monoclonal Antibody (antibody)
RRID:AB_560835
This monoclonal targets 4E-BP1, phospho (Thr37 / Thr46)
View all literature mentionsRat Anti-BrdU Monoclonal Antibody, Unconjugated, Clone BU1 / 75 (ICR1) (antibody)
RRID:AB_305426
This monoclonal targets BrdU
View all literature mentionsRabbit Anti-Histone H3, phospho (Ser10) Monoclonal Antibody, Unconjugated, Clone D2C8 (antibody)
RRID:AB_1549592
This monoclonal targets Histone H3, phospho (Ser10)
View all literature mentionsNeuroD2 antibody (antibody)
RRID:AB_10975628
This polyclonal targets NeuroD2 antibody
View all literature mentionsEOMES Monoclonal Antibody (Dan11mag), eBioscience (antibody)
RRID:AB_11042577
This monoclonal targets EOMES
View all literature mentionsRabbit Anti-Mouse TBR2 / Eomes Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_778267
This polyclonal targets Mouse TBR2 / Eomes
View all literature mentionsRabbit Anti-PAX6 , Unconjugated (antibody)
RRID:AB_1587367
This unknown targets PAX6
View all literature mentionsHuman/Mouse/Rat SOX2 Antibody (antibody)
RRID:AB_355110
This polyclonal targets SOX2
View all literature mentionsSox2 (C70B1) Rabbit mAb (IHC Preferred) (antibody)
RRID:AB_2194037
This monoclonal targets Sox2 (C70B1)
View all literature mentionsNeuro-2a (cell line)
RRID:CVCL_0470
Cell line Neuro-2a is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsHEK293 (cell line)
RRID:CVCL_0045
Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentions
