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

Border-associated macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia

“…1J; Supplemental Video 2 ). Taken together, these data support the recently provided model that BAMs infiltrate the embryonic brain to contribute to the microglial lineage (Green et al ., 2022; Masuda et al ., 2022), newly suggesting that the ventricle-to-pallium infiltration of BAMs could be one of the possible routes for microglial colonization into the cerebral wall ( Fig. 1K ).…”

“…This study supports a recently provided model in which brain microglia are not only derived from yolk sac progenitors committed early but also supplied later during brain development/maturation from macrophages (Green et al ., 2022; Masuda et al ., 2022). Despite observations that postnatal mouse BAMs infiltrate along blood vessels to become perivascular macrophages (Masuda et al ., 2022) and that lymphatic vessels assist in BAM colonization into the embryonic zebrafish brain (Green et al ., 2022), how BAMs actually enter the developing brain parenchyma, i.e., what cellular routes are used, remains to be elucidated.…”

“…This study supports a recently provided model in which brain microglia are not only derived from yolk sac progenitors committed early but also supplied later during brain development/maturation from macrophages (Green et al ., 2022; Masuda et al ., 2022). Despite observations that postnatal mouse BAMs infiltrate along blood vessels to become perivascular macrophages (Masuda et al ., 2022) and that lymphatic vessels assist in BAM colonization into the embryonic zebrafish brain (Green et al ., 2022), how BAMs actually enter the developing brain parenchyma, i.e., what cellular routes are used, remains to be elucidated. Here, we showed a transventricular mechanism: E12.5 mouse cerebral hemispheres allow externally localized BAMs to migrate first into the ventricle across the roof plate and further into the pallial wall, which is a temporally regulated physiological set of phenomena to seed embryonic mouse microglia and may be relevant to a recent observation of the inflammation-induced aberrant recruitment of intraventricular macrophages into the mouse brain parenchyma at E15.5 (Cui et al ., 2020).…”

“…Similar competence for flexible differentiation in CD206 + lineage cells has previously been suggested in tissue-resident macrophages (Mass et al, 2016). Recently, another fate-tracking study by Green et al in zebrafish showed that BAMs indeed contribute to seeding a certain fraction of the total microglial population (Green et al, 2022). The authors further found that the source of BAMs to be used for microglial seeding via fate conversion is the brain-surrounding lymphatic vessels, although how BAM infiltration into brains actually occurs remains unknown.…”

A developmental atlas of the mouse brain by single-cell mass cytometry

“…Beyond supporting the existence of EMP-like cells in embryonic mouse brain as early as E11.5, our results show that CD45 high PECAM high cells persist thereafter into the perinatal period at relative abundances that mimicked expansion of endothelial and hematopoietic cells in each brain region. These results are reminiscent of recent findings showing that a lymphatic-derived microglial population seeds the zebrafish brain prior to colonization by yolk sac-derived microglia and persists thereafter until at least the juvenile stage 146 . Accordingly, the extent to which this putative stem cell pool contributes to erythroid, myeloid, and/or endothelial progeny during mouse brain development is a promising area of inquiry for future studies.…”