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Updated: Aug 17, 2026
Identification Of Erythromyeloid Progenitors And Their Progeny In The Mouse Embryo By Flow Cytometry
Published on: July 17, 2017
Three pathways to mature macrophages in the early mouse yolk sac
Julien Y Bertrand1, Abdelali Jalil, Michèle Klaine
1Institut National de la Santé et de la Recherche Médicale (INSERM) U668, Unité de Développement des Lymphocytes, Institut Pasteur, Paris, France.
Abstract:
The existence of macrophages (Mphi) of yolk-sac (YS) origin has been reported in all vertebrate models. However, the nature of their precursors and pathways of differentiation have not been elucidated. Phenotypic and differentiation potential analyses of YS at 7.5 to 10 postcoital days (dpc), performed in CX3CR1(GFP) embryos, allowed us to discern 3 independent Mphi populations. A first transient wave consisted of mature, maternal-derived Mphipresent as early as 7.5 to 8 dpc. A second wave of committed Mphi precursors arose at 8 dpc (2-4 somite stage) and was followed by a third wave of erythromyeloid precursors (4-6 somite stage). Both types of precursors displayed similar phenotypes and gave rise to CX3CR1/green fluorescent protein (GFP)-positive Mphi, but differed by their differentiation potential, at the clonal level. The combined data of phenotypic, gene-expression, and in situ analyses allowed us to conclude that the previously named "primitive Mphi" corresponded to a mixture of the first transient wave and committed Mphi precursors. Both YS-derived precursors followed a developmental pathway common to adult Mphi and could be qualified as definitive.
Insights
Macrophages originating from the yolk sac (YS) have diverse precursors. This study identifies three distinct macrophage populations, clarifying their developmental pathways and definitive nature in vertebrate models.
Area of Science:
- Developmental Biology
- Immunology
- Hematopoiesis
Background:
- Macrophages (Mphi) of yolk-sac (YS) origin are present in all vertebrates.
- The precise nature of their precursors and differentiation pathways remain unclear.
Purpose of the Study:
- To investigate the origins and differentiation pathways of yolk-sac derived macrophages.
- To characterize distinct macrophage precursor populations in early embryonic development.
Main Methods:
- Analysis of yolk sacs from CX3CR1(GFP) embryos at 7.5 to 10 postcoital days (dpc).
- Phenotypic analysis, differentiation potential assays (clonal level), gene-expression profiling, and in situ hybridization.
Main Results:
- Identified three independent macrophage populations: a transient maternal wave, committed Mphi precursors, and erythromyeloid precursors.
- YS-derived precursors share a common developmental pathway with adult macrophages.
- Previously termed 'primitive Mphi' are a mix of maternal Mphi and committed YS precursors.
Conclusions:
- Yolk sac-derived precursors are definitive macrophages.
- Clarified the heterogeneity and developmental trajectory of early embryonic macrophages.
