期刊
DEVELOPMENT
卷 145, 期 13, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.152306
关键词
Tmem119; Microglia; Hoxb8 microglia; Non-Hoxb8 microglia; Microglia ontogeny; Yolk sac; AGM and fetal liver hematopoiesis; Fetal HSCs; OCD; Obsessive-compulsive-spectrum disorders; Trichotillomania
资金
- Foundation for the National Institutes of Health [R01 MH093595]
- National Cancer Institute [5P30CA042014-24]
- National Center for Research Resources [1S10RR026802-01]
- University of Utah Flow Cytometry Facility
- NATIONAL CANCER INSTITUTE [P30CA042014] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR026802] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH093595] Funding Source: NIH RePORTER
Hoxb8 mutant mice show compulsive behavior similar to trichotillomania, a human obsessive-compulsive-spectrum disorder. The only Hoxb8 lineage-labeled cells in the brains of mice are microglia, suggesting that defective Hoxb8 microglia caused the disorder. What is the source of the Hoxb8 microglia? It has been posited that all microglia progenitors arise at embryonic day (E) 7.5 during yolk sac hematopoiesis, and colonize the brain at E9.5. In contrast, we show the presence of two microglia subpopulations: canonical, non-Hoxb8 microglia and Hoxb8 microglia. Unlike non-Hoxb8 microglia, Hoxb8 microglia progenitors appear to be generated during the second wave of yolk sac hematopoiesis, then detected in the aorto-gonad-mesonephros (AGM) and fetal liver, where they are greatly expanded, prior to infiltrating the E12.5 brain. Further, we demonstrate that Hoxb8 hematopoietic progenitor cells taken from fetal liver are competent to give rise to microglia in vivo. Although the two microglial subpopulations are very similar molecularly, and in their response to brain injury and participation in synaptic pruning, they show distinct brain distributions which might contribute to pathological specificity. Non-Hoxb8 microglia significantly outnumber Hoxb8 microglia, but they cannot compensate for the loss of Hoxb8 function in Hoxb8 microglia, suggesting further crucial differences between the two subpopulations.
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