Zebrafish as a model for leukemia and other hematopoietic disorders

Abstract

Zebrafish is an established model for the study of vertebrate development, and is especially amenable for investigating hematopoiesis, where there is strong conservation of key lineages, genes, and developmental processes with humans. Over recent years, zebrafish has been increasingly utilized as a model for a range of human hematopoietic diseases, including malignancies. This review provides an overview of zebrafish hematopoiesis and describes its application as a model of leukemia and other hematopoietic disorders.

Figure 1

Zebrafish hematopoiesis and its key regulators. Schematic representation of hematopoiesis in zebrafish. The primitive wave commences in two locations, the anterior lateral mesoderm (ALM) (orange), which gives rise to primitive monocytes, and the intermediate cellular mass (ICM) (violet), which generates mostly primitive erythrocytes before 24 hpf. A transient ‘intermediate’ wave occurs in the posterior blood island (PBI) where both erythrocytes and heterophils are formed (grey). Definitive hematopoietic stem cells (HSCs) are initially formed by budding from the hemogenic endothelium on the ventral wall of dorsal aorta (blue). A subset of these HSCs migrate to the caudal hematopoietic tissue (CHT) (yellow) to produce several cell lineages, and also the thymus (purple), where T lymphocyte production occurs. Finally, HSCs seed the developing kidney (green), the final site of definitive hematopoiesis where erythroid, myeloid, and B lymphocyte production occurs. The lineage-specific transcription factors that serve to regulate this process are in red. Abbreviations: BP: B cell progenitor, CLP: common lymphoid progenitor, CMP: common myeloid progenitor, EP: erythroid progenitor, Ery: erythrocyte, GMP: granulocyte-monocyte progenitor, Hemangio: hemangioblast, Hetero: heterophil, HSC: hematopoietic stem cell, Mono: monocyte, TP: T cell progenitor.