Zebrafish Early Macrophages Colonize Cephalic Mesenchyme and Developing Brain, Retina, and Epidermis through a M-CSF Receptor-Dependent Invasive Process

0301 basic medicine Superior Colliculi Time Factors fms microglia Down-Regulation Receptor, Macrophage Colony-Stimulating Factor M-CSF/CSF-1 macrophage motility Models, Biological Retina Mesoderm 03 medical and health sciences Apolipoproteins E epidermis Animals Molecular Biology In Situ Hybridization Zebrafish apolipoprotein E Membrane Glycoproteins Macrophages Microfilament Proteins Brain Cell Biology zebrafish Phosphoproteins macrophages Phenotype Mutation embryogenesis Epidermis Developmental Biology
DOI: 10.1006/dbio.2001.0393 Publication Date: 2002-09-16T15:45:48Z
ABSTRACT
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 macrophages spread in the whole cephalic mesenchyme, and from there invade epithelial tissues: epidermis, retina, and brain--especially the optic tectum. In the panther mutant, which lacks a functional fms (M-CSF receptor) gene, early macrophages differentiate and behave apparently normally in the yolk sac, but then fail to invade embryonic tissues. Our video recordings then document for the first time the behavior of macrophages in the invaded tissues, revealing the striking propensity of early macrophages in epidermis and brain 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-fertilization, all macrophages in the brain and retina undergo a specific phenotypic transformation, into "early (amoeboid) microglia": they become more highly endocytic, they down-regulate the L-plastin gene, and abruptly start expressing high levels of apolipoprotein E, a well-known neurotrophic lipid carrier.
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