Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals.

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 Sp

SUBMITTER: Wu Y 

PROVIDER: S-EPMC12270482 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature