PT - JOURNAL ARTICLE AU - Laura E. Kuil AU - Nynke Oosterhof AU - Giuliano Ferrero AU - Tereza Mikulášová AU - Martina Hason AU - Jordy Dekker AU - Mireia Rovira AU - Herma C. van der Linde AU - Paulina M.H. van Strien AU - Emma de Pater AU - Gerben Schaaf AU - Eric M.J. Bindels AU - Valerie Wittamer AU - Tjakko J. van Ham TI - Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes AID - 10.1101/2020.04.04.025585 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.04.04.025585 4099 - http://biorxiv.org/content/early/2020/04/05/2020.04.04.025585.short 4100 - http://biorxiv.org/content/early/2020/04/05/2020.04.04.025585.full AB - Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the absence of CSF1R. Here, we analyzed mpeg1:GFP–expressing macrophages in csf1r-deficient zebrafish and report that embryonic macrophages emerge followed by their developmental arrest. In larvae, mpeg1+ cell numbers then increased showing two distinct types in the skin: branched, putative Langerhans cells, and amoeboid cells. In contrast, although numbers also increased in csf1r-mutants, exclusively amoeboid mpeg1+ cells were present, which we showed by genetic lineage tracing to have a non-hematopoietic origin. They expressed macrophage-associated genes, but also showed decreased phagocytic gene expression and increased epithelial-associated gene expression, characteristic of metaphocytes, recently discovered ectoderm-derived cells. We further demonstrated that juvenile csf1r-deficient zebrafish exhibit systemic macrophage depletion. Thus, Csf1r deficiency disrupts embryonic to adult macrophage development. Csf1r-deficient zebrafish are viable and permit analyzing the consequences of macrophage loss throughout life.