The embryonic zebrafish brain is seeded by a lymphatic-dependent population of mrc1+ microglia precursors

Microglia are the resident macrophages of the CNS that serve critical roles in brain construction. Although human brains contain microglia by 4 weeks gestation, an understanding of the earliest microglia that seed the brain during its development remains unresolved. Using time-lapse imaging in zebra...

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Bibliographic Details
Published in:Nature neuroscience 2022-07, Vol.25 (7), p.849-864
Main Authors: Green, Lauren A., O’Dea, Michael R., Hoover, Camden A., DeSantis, Dana F., Smith, Cody J.
Format: Article
Language:English
Subjects:
631/136/142
631/378/2571/219
631/378/2596/1953
Animal Genetics and Genomics
Animals
Behavioral Sciences
Biological Techniques
Biomedical and Life Sciences
Biomedicine
Brain
Brain - physiology
Danio rerio
Embryos
Gene sequencing
Humans
Lymphatic system
Macrophages
Microglia
Microglia - metabolism
Neurobiology
Neuroimaging
Neurosciences
Precursors
Seeds
Yolk sac
Yolk Sac - metabolism
Zebrafish
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
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Summary:Microglia are the resident macrophages of the CNS that serve critical roles in brain construction. Although human brains contain microglia by 4 weeks gestation, an understanding of the earliest microglia that seed the brain during its development remains unresolved. Using time-lapse imaging in zebrafish, we discovered a mrc1a + microglia precursor population that seeds the brain before traditionally described microglia. These early microglia precursors are dependent on lymphatic vasculature that surrounds the brain and are independent of pu1 + yolk sac-derived microglia. Single-cell RNA-sequencing datasets reveal Mrc1 + microglia in the embryonic brains of mice and humans. We then show in zebrafish that these early mrc1a + microglia precursors preferentially expand during pathophysiological states in development. Taken together, our results identify a critical role of lymphatics in the microglia precursors that seed the early embryonic brain. Green and O’Dea et al. identify that the embryonic zebrafish brain is colonized by a population of early-colonizing microglia that are dependent on lymphatic vessels, placing lymphatic cells at the epicenter of microglia development.
ISSN:1097-6256
1546-1726
DOI:10.1038/s41593-022-01091-9