PUBLICATION
Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals
- Authors
- Wu, Y., Guo, W., Kuang, H., Wu, X., Trinh, T.H., Wang, Y., Zhao, S., Wen, Z., Yu, T.
- ID
- ZDB-PUB-250718-1
- Date
- 2025
- Source
- eLIFE 14: (Journal)
- Registered Authors
- YU, Tao
- Keywords
- cell competition, developmental biology, maintenance, microglia, mouse, pu.1 dosage, turnover, zebrafish
- Datasets
- GEO:GSE283170
- MeSH Terms
-
- Microglia*/cytology
- Microglia*/metabolism
- Proto-Oncogene Proteins*/metabolism
- Zebrafish*
- Male
- Trans-Activators*/metabolism
- Mice
- Mammals/metabolism
- Animals
- PubMed
- 40673490 Full text @ Elife
Citation
Wu, Y., Guo, W., Kuang, H., Wu, X., Trinh, T.H., Wang, Y., Zhao, S., Wen, Z., Yu, T. (2025) Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals. eLIFE. 14:.
Abstract
Microglia are brain-resident macrophages playing pivotal roles in central nervous system (CNS) development and homeostasis. Yet, the cellular and molecular basis governing microglia maintenance remains largely unknown. Here, by utilizing a visible conditional knockout allele of pu.1/spi1b gene (the master regulator for microglia/macrophage lineage development) to generate mosaic microglia populations in adult zebrafish, we show that while pu.1-deficient microglia are immediately viable, they are less competitive, and chronically eliminated through Tp53-mediated cell competition. Interestingly, when conditionally inactivating Pu.1 in adult spi-b (the orthologue of mouse Spi-b) null mutants, microglia are rapidly depleted via apoptosis, suggesting that Pu.1 and Spi-b regulate microglia maintenance in a dosage-dependent manner. The dosage-dependent regulation of microglia maintenance by PU.1/SPI1 is evolutionarily conserved in mice, as shown by conditionally inactivating single and both Spi1 alleles in microglia, respectively. Collectively, our study reveals the conserved cellular and molecular mechanisms controlling microglia turnover and maintenance in teleosts and mammals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping