Zebrafish early macrophages colonize cephalic mesenchyme and developing brain, retina, and epidermis through, a M-CSF receptor-dependent invasive process

The origin of resident (noninflammatory) macrophages in vertebrate tissues is still poorly understood. In the zebrafish embryo, we recently described a specific lineage of early macrophages that differentiate in the yolk sac before the onset of blood circulation. We now show that these early macroph ages spread in the whole cephalic mesenchyme, and from there invade epithel ial tissues: epidermis, retina, and brain-especially the optic tectum. In t he panther mutant, which lacks: a functional fins (M-CSF receptor) gene, ea rly macrophages differentiate and behave apparently normally in the yolk sa c, but then fail to invade embryonic tissues. Our video recordings then doc ument for the first time the behavior of macrophages in the invaded tissues , revealing the striking propensity of early macrophages in epidermis and b rain to wander restlessly among epithelial cells. This unexpected behavior suggests that tissue macrophages may be constantly "patrolling" for immune and possibly also developmental and trophic surveillance. At 60 h post-fert ilization, all macrophages in the brain and retina undergo a specific pheno typic transformation, into "early (amoeboid) microglia": they become more h ighly endocytic, they down-regulate the L-plastin gene, and abruptly start expressing high levels of apolipoprotein E, a well-known neurotrophic lipid carrier. (C) 2001 Academic Press.