In the zebrafish embryo, the only known site of hemopoieisis is an intra-em
bryonic blood island at the junction between trunk and tail that gives rise
to erythroid cells, Using video-enhanced differential interference contras
t microscopy, as well as in-situ hybridization for the expression of two ne
w hemopoietic marker genes, draculin and leucocyte-specific plastin, we sho
w that macrophages appear in the embryo at least as early as erythroid cell
s, but originate from ventrolateral mesoderm situated at the other end of t
he embryo, just anterior to the cardiac field. These macrophage precursors
migrate to the yolksac, and differentiate. From the yolksac, many invade th
e mesenchyme of the head, while others join the blood circulation, Apart fr
om phagocytosing apoptotic corpses, these macrophages were observed to engu
lf and destroy large amounts of bacteria injected intravenously; the macrop
hages also sensed the presence of bacteria injected into body cavities that
are isolated from the blood, migrated into these cavities and eradicated t
he microorganisms. Moreover, we observed that although only a fraction of t
he macrophage population goes to the site of infection, the entire populati
on acquires an activated behaviour, similar to that of activated macrophage
s in mammals, Our results support the notion that in vertebrate embryos, ma
crophages endowed with proliferative capacity arise early from the hemopoie
tic lineage through a nonclassical, rapid differentiation pathway, which by
passes the monocytic series that is well-documented in adult. hemopoietic o
rgans.