The progress and promise of zebrafish as a model to study mast cells

•Unique features of the vertebrate immune system are the presence of immunoglobulins and mast cells.•Mast cells are an ancient cell type present in all vertebrates and some chordates.•Mast cells function in the immune system and their deregulation is implicated in disease.•In zebrafish, cpa5 is a mast-cell-specific marker gene useful for labeling mast cells. Immunological and hematological research using the zebrafish (Danio rerio) has significantly advanced our understanding of blood lineage ontology, cellular functions and mechanisms, and provided opportunities for disease modeling. Mast cells are an immunological cell type involved in innate and adaptive immune systems, hypersensitivity reactions and cancer progression. The application of zebrafish to study mast cell biology exploits the developmental and imaging opportunities inherent in this model system to enable detailed genetic and molecular studies of this lineage outside of traditional mammalian models. In this review, we first place the importance of mast cell research in zebrafish into the context of comparative studies of mast cells in other fish species and highlight its advantages due to superior experimental tractability and direct visualization in transparent embryos. We discuss current and future tools for mast cell research in zebrafish and the notable results of using zebrafish for understanding mast cell fate determination and our development of a systemic mastocytosis model.