Dendritic cells in developing and adult zebrafish arise from different origins and display distinct flt3 dependencies

Dendritic cells (DCs) are key cellular components of the immune system and perform critical functions in innate and acquired immunity. In mammals, it is generally believed that DCs originate exclusively from hematopoietic stem cells (HSCs). Using a temporal-spatial resolved fate-mapping system, here we show that in zebrafish, DCs arise from two sources: dorsal aorta-born endothelium-derived hematopoietic progenitors (EHPs) and HSCs. The EHP-derived DCs emerge early, predominantly colonizing the developing thymus during larval stages and diminishing by juvenile stages. In contrast, HSC-derived DCs emerge later and can populate different tissues from late larval stages to adulthood. We further document that the EHP- and HSC-derived DCs display different dependencies on Fms-like tyrosine kinase 3 (Flt3), a pivotal receptor tyrosine kinase crucial for DC development in mammals. Our study reveals the presence of two distinct waves of DC development in zebrafish, each with unique origins and developmental controls.