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Artikel: Dephosphorylation of 4EBP1/2 Induces Prenatal Neural Stem Cell Quiescence.

Geben, Laura C / Brockman, Asa A / Chalkley, Mary Bronwen L / Sweet, Serena R / Gallagher, Julia E / Scheuing, Alexandra L / Simerly, Richard B / Ess, Kevin C / Irish, Jonathan M / Ihrie, Rebecca A

bioRxiv : the preprint server for biology

2023  

Abstract: A limiting factor in the regenerative capacity of the adult brain is the abundance and proliferative ability of neural stem cells (NSCs). Adult NSCs are derived from a subpopulation of embryonic NSCs that temporarily enter quiescence during mid-gestation ...

Abstract A limiting factor in the regenerative capacity of the adult brain is the abundance and proliferative ability of neural stem cells (NSCs). Adult NSCs are derived from a subpopulation of embryonic NSCs that temporarily enter quiescence during mid-gestation and remain quiescent until postnatal reactivation. Here we present evidence that the mechanistic/mammalian target of rapamycin (mTOR) pathway regulates quiescence entry in embryonic NSCs of the developing forebrain. Throughout embryogenesis, two downstream effectors of mTOR, p-4EBP1/2 T37/46 and p-S6 S240/244, were mutually exclusive in NSCs, rarely occurring in the same cell. While 4EBP1/2 was phosphorylated in stem cells undergoing mitosis at the ventricular surface, S6 was phosphorylated in more differentiated cells migrating away from the ventricle. Phosphorylation of 4EBP1/2, but not S6, was responsive to quiescence induction in cultured embryonic NSCs. Further, inhibition of p-4EBP1/2, but not p-S6, was sufficient to induce quiescence. Collectively, this work offers new insight into the regulation of quiescence entry in embryonic NSCs and, thereby, correct patterning of the adult brain. These data suggest unique biological functions of specific posttranslational modifications and indicate that the preferential inhibition of such modifications may be a useful therapeutic approach in neurodevelopmental diseases where NSC numbers, proliferation, and differentiation are altered.
Sprache Englisch
Erscheinungsdatum 2023-02-15
Erscheinungsland United States
Dokumenttyp Preprint
DOI 10.1101/2023.02.14.528513
Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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