Genome integrity and neurogenesis of postnatal hippocampal neural stem/progenitor cells require a unique regulator Filia.

Abstract

Endogenous DNA double-strand breaks (DSBs) formation and repair in neural stem/progenitor cells (NSPCs) play fundamental roles in neurogenesis and neurodevelopmental disorders. NSPCs exhibit heterogeneity in terms of lineage fates and neurogenesis activity. Whether NSPCs also have heterogeneous regulations on DSB formation and repair to accommodate region-specific neurogenesis has not been explored. Here, we identified a regional regulator Filia, which is predominantly expressed in mouse hippocampal NSPCs after birth and regulates DNA DSB formation and repair. On one hand, Filia protects stalling replication forks and prevents the replication stress-associated DNA DSB formation. On the other hand, Filia facilitates the homologous recombination-mediated DNA DSB repair. Consequently, Filia-/- mice had impaired hippocampal NSPC proliferation and neurogenesis and were deficient in learning, memory, and mood regulations. Thus, our study provided the first proof of concept demonstrating the region-specific regulations of DSB formation and repair in subtypes of NSPCs.

• Authors: Jingzheng Li, Yafang Shang, Lin Wang, Bo Zhao, Chunli Sun, Jiali Li, Siling Liu, Cong Li, Min Tang, Fei-Long Meng, Ping Zheng
• Journal: Science advances (Sci Adv) Vol. 6 Issue 44 (10 2020) ISSN: 2375-2548 [Electronic] United States
• PMID: 33115731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Chemical References

• Proteins
• filia protein, mouse

Topics

• Animals
• DNA Breaks, Double-Stranded
• Hippocampus
• Mice
• Neural Stem Cells
• Neurogenesis
• Proteins (genetics)