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The Mouse Hindbrain As a Model for Studying Embryonic Neurogenesis
Published on: January 29, 2018
Neural progenitor cells mediated by H2A.Z.2 regulate microglial development via Cxcl14 in the embryonic brain
Zhongqiu Li1,2, Yanxin Li1,2, Jianwei Jiao3,2,4
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Abstract:
Microglia, the resident immune cells of the central nervous system, play an important role in the brain. Microglia have a special spatiotemporal distribution during the development of the cerebral cortex. Neural progenitor cells (NPCs) are the main source of neural-specific cells in the early brain. It is unclear whether NPCs affect microglial development and what molecular mechanisms control early microglial localization. H2A.Z.2, a histone variant of H2A, has a key role in gene expression regulation, genomic stability, and chromatin remodeling, but its function in brain development is not fully understood. Here, we found that the specific deletion of H2A.Z.2 in neural progenitor cells led to an abnormal increase in microglia in the ventricular zone/subventricular zone (VZ/SVZ) of the embryonic cortex. Mechanistically, H2A.Z.2 regulated microglial development by incorporating G9a into the promoter region of Cxcl14 and promoted H3k9me2 modification to inhibit the transcription of Cxcl14 in neural progenitor cells. Meanwhile, we found that the deletion of H2A.Z.2 in microglia itself had no significant effect on microglial development in the early cerebral cortex. Our findings demonstrate a key role of H2A.Z.2 in neural progenitor cells in controlling microglial development and broaden our knowledge of 2 different types of cells that may affect each other through crosstalk in the central nervous system.
Insights
Neural progenitor cells control microglial development via H2A.Z.2. Deleting H2A.Z.2 in neural progenitor cells alters microglia localization in the embryonic brain, revealing cell crosstalk mechanisms.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia are key immune cells in the central nervous system with critical roles in brain development.
- Neural progenitor cells (NPCs) are the primary source of neurons during early brain formation.
- The interaction between NPCs and microglia during early cortical development is not fully understood.
Purpose of the Study:
- To investigate the role of histone variant H2A.Z.2 in neural progenitor cells on microglial development and localization.
- To elucidate the molecular mechanisms by which neural progenitor cells influence early microglial distribution.
- To determine if H2A.Z.2 in microglia impacts their own development.
Main Methods:
- Utilized genetic deletion of H2A.Z.2 specifically in neural progenitor cells in a mouse model.
- Analyzed microglial distribution in the embryonic cortex, particularly in the ventricular zone/subventricular zone (VZ/SVZ).
- Investigated the molecular regulation of Cxcl14 gene expression by H2A.Z.2 in NPCs, including G9a incorporation and H3k9me2 modification.
Main Results:
- Specific deletion of H2A.Z.2 in NPCs caused an abnormal accumulation of microglia in the embryonic cortex VZ/SVZ.
- H2A.Z.2 in NPCs regulates microglial development by influencing Cxcl14 transcription through G9a and H3k9me2 modification.
- H2A.Z.2 deletion within microglia themselves did not significantly affect their development in the early cerebral cortex.
Conclusions:
- H2A.Z.2 in neural progenitor cells plays a crucial role in controlling microglial development and localization during embryonic brain development.
- This study reveals a novel mechanism of intercellular communication, highlighting the crosstalk between NPCs and microglia in the CNS.
- The findings expand our understanding of the complex regulatory networks governing early brain development and immune cell interactions.
