A macrophage subpopulation promotes airineme-mediated intercellular communication in a Matrix Metalloproteinase-9-dependent manner
Tissue-resident macrophages are highly heterogenous and perform various dedicated functions depending on their locations. In particular, skin resident macrophages have intriguing roles in long-distance intercellular signaling by mediating cellular protrusions called airinemes in zebrafish. During pigment pattern formation, macrophages relay signaling molecules containing airineme vesicles from one pigment cell to another. Without macrophages, airineme-mediated signaling is abolished, disrupting pigment pattern formation. It remains unknown, however, if the same macrophage population controls both these signaling roles and typical immune functions or if a separate macrophage subpopulation functions in intercellular communication. In this study, with high-resolution confocal live-imaging and cell type-specific genetic ablation approaches in vivo, we have identified a macrophage subpopulation responsible for airineme-mediated signaling. These cells appear distinct from conventional skin resident macrophages by their amoeboid morphology and faster/expansive migratory behaviors. Instead, we show that they resemble ectoderm-derived macrophages termed metaphocytes. Metaphocyte ablation dramatically reduces airineme extension and signaling. In addition, these amoeboid/metaphocytes require high levels of MMP9 expression for their migration and airineme-mediated signaling. These results reveal a novel macrophage subpopulation with specialized functions in airineme-mediated signaling, which may play roles in many other aspects of intercellular communication.