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Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 127-138
Differentiation of the Mononuclear Phagocyte System During Mouse
Embryogenesis: The Role of Transcription Factor PU.1
Agnieszka M. Lichanska,
Catherine M. Browne,
Gregory W. Henkel,
Kathleen M. Murphy,
Michael C. Ostrowski,
Scott R. McKercher,
Richard A. Maki, and
David A. Hume
From the Departments of Microbiology and Biochemistry and Centre for
Molecular and Cellular Biology, University of Queensland, Queensland,
Australia; the Department of Molecular Genetics, Ohio State University,
Columbus, OH; and the Burnham Institute, La Jolla, CA.
During mouse embryogenesis, macrophage-like cells arise first in the
yolk sac and are produced subsequently in the liver. The onset of liver
hematopoiesis is associated with the transition from primitive to
definitive erythrocyte production. This report addresses the hypothesis
that a similar transition in phenotype occurs in myelopoiesis. We have
used whole mount in situ hybridization to detect macrophage-specific
genes expressed during mouse development. The mouse c-fms mRNA,
encoding the receptor for macrophage colony-stimulating factor (CSF-1),
was expressed on phagocytic cells in the yolk sac and throughout the
embryo before the onset of liver hematopoiesis. Similar cells were
detected using the mannose receptor, the complement receptor (CR3), or
the Microphthalmia transcription factor (MITF) as mRNA markers.
By contrast, other markers including the F4/80 antigen, the macrophage
scavenger receptor, the S-100 proteins, S100A8 and S100A9, and the
secretory product lysozyme appeared later in development and appeared
restricted to only a subset of c-fms-positive cells. Two-color
immunolabeling on disaggregated cells confirmed that CR3 and c-fms
proteins are expressed on the same cells. Among the genes
appearing later in development was the macrophage-restricted
transcription factor, PU.1, which has been shown to be required for
normal adult myelopoiesis. Mice with null mutations in PU.1 had normal
numbers of c-fms-positive phagocytes at 11.5dpc. PU.1( /)
embryonic stem cells were able to give rise to macrophage-like cells
after cultivation in vitro. The results support previous evidence that
yolk sac-derived fetal phagocytes are functionally distinct from those
arising in the liver and develop via a different pathway.
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