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

  • Nat Neurosci. 2022 Jul;25(7):849-864. doi: 10.1038/s41593-022-01091-9.
Lauren A Green   #  1  2 ,  Michael R O'Dea   #  1 ,  Camden A Hoover  1  2 ,  Dana F DeSantis  1  2 ,  Cody J Smith  3  4
Affiliations
  • 1. Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
  • 2. The Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN, USA.
  • 3. Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA. [email protected].
  • 4. The Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN, USA. [email protected].
  • # Contributed equally.
PMID: 35710983 DOI: 10.1038/s41593-022-01091-9
Abstract

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.

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