1. Academic Validation
  2. The embryonic zebrafish brain is seeded by a lymphatic-dependent population of mrc1+ microglia precursors

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

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.
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.

Figures
Products