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
AUTHORS (3)
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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