To better understand the distinct functions of yolk-sac-derived tissue-resident macrophages (TRMs) and bone-marrow-derived macrophages in homeostasis and disease, it is important to trace the ontogeny of these cells. The majority of TRMs originate from erythro-myeloid progenitors (EMPs). EMPs develop into pre-macrophages (pMacs), which can be detected starting at embryonic developmental day (E)9.0, and which give rise to all TRM during early development. pMacs start expressing the gene Cx3cr1, allowing us to genetically target the early yolk-sac wave of pMacs and their progeny. Here, we describe the protocol for the identification of yolk sac-derived TRMs utilizing in utero labelling of the inducible fate mapping Cx3cr1; Rosa26 mouse model.
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