No abstract

Microglia are CNS resident macrophages, and they play important roles in neural development and function. Recent studies have suggested that murine microglia arise from a single source, the yolk sac (YS), yet these studies lack spatial resolution to define the bona fide source(s) for microglia. Here, using light-induced high temporal-spatial resolution fate mapping, we challenge this single-source view by showing that microglia in zebrafish arise from multiple sources. The embryonic/larval microglia originate from the rostral blood island (RBI) region, the equivalent of mouse YS for myelopoiesis, whereas the adult microglia arise from the ventral wall of dorsal aorta (VDA) region, a tissue also producing definitive hematopoiesis in mouse. We further show that the VDA-region-derived microglia are Runx1 dependent, but cMyb independent, and developmentally regulated differently from the RBI region-derived microglia. Our study establishes a new paradigm for investigating the development and function of distinct microglia populations.

The origin of Langerhans cells (LCs), which are skin epidermis-resident macrophages, remains unclear. Current lineage tracing of LCs largely relies on the promoter-Cre-LoxP system, which often gives rise to contradictory conclusions with different promoters. Thus, reinvestigation with an improved tracing method is necessary. Here, using a laser-mediated temporal-spatial resolved cell labeling method, we demonstrated that most adult LCs originated from the ventral wall of the dorsal aorta (VDA), an equivalent to the mouse aorta, gonads, and mesonephros (AGM), where both hematopoietic stem cells (HSCs) and non-HSC progenitors are generated. Further fine-fate mapping analysis revealed that the appearance of LCs in adult zebrafish was correlated with the development of HSCs, but not T cell progenitors. Finally, we showed that the appearance of tissue-resident macrophages in the brain, liver, heart, and gut of adult zebrafish was also correlated with HSCs. Thus, the results of our study challenged the EMP-origin theory for LCs.