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. 2019 Nov 26;25(2):351–367. doi: 10.1038/s41380-019-0609-8

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — Possible different regional ontogenesis and entry routes of microglia in the developing mouse brain. Microglia, along with other tissue macrophages, are generated in successive waves of myelogenesis during mouse embryonic (E) development. The first wave of microglia is generated by Runx- and Csf1r-dependent, cMyb-independent primitive macrophages (PMs) in the yolk sac (YS) at E7.5, whilst the second wave is generated by cMyb-dependent erythromyeloid progenitors (EMPs) at E8.25 from the YS as well as the aorta–gonad–mesonephros (AGM) and fetal liver at E8.25-E10, during which definitive hematopoiesis happens. Adult microglial (or microglia-like) cells may also come from cMyb-dependent fetal liver monocytes in mouse [141] and embryonic hematopoietic stem cells (HSCs) in zebrafish [94]. A transient appearance of fetal liver-derived microglia in the neonate mouse brain was also found [46]. Microglial precursors from the primitive and definitive waves migrate into the brain at E9.5 and self-sustain throughout adulthood [91, 92]. It is possible that microglia deriving from different origins and in different waves may enter and occupy different niches in the developing brain. For example, Hoxb8⁻ and Hoxb⁺ microglia came from primitive and definitive hematopoiesis, respectively, and infiltrated the brain at different E stages in different brain areas [101]