Beyond Immunity: Macrophages as Regulators of Vertebrate Morphogenesis

Research over the last decades have demonstrated that macrophages, considered canonical players of the immune system, also perform many other important biological functions in adult organisms. These properties have stimulated extensive research, particularly given their importance in human pathologies, including cancer. However, despite significant advances in our understanding of macrophage functions in adult organisms and diseases, their roles in embryonic systems remain comparatively underexplored. Owing to their complex developmental origin and the lack of pronounced phenotypes in embryos subjected to either spontaneous or experimentally induced macrophage ablation, macrophages have often been considered as a largely passive scavenger population associated with programmed cell death during organ and tissue remodeling. Here, we highlight key findings regarding macrophage functions during vertebrate morphogenesis. We emphasize the differences in phenotypic outcomes following macrophage ablation in adult organisms, embryos, and models of organ regeneration. Currently, the remarkable plasticity of the macrophage lineage complicates the identification of specific trophic functions involved in organ morphogenesis. Developing new approaches that improve the efficiency of macrophage ablation models, along with implementing complementary gain-of-function strategies, will contribute to a deeper understanding of the role of macrophages during embryonic development.