Dissecting hematopoiesis and disease using the zebrafish

The study of blood has often defined paradigms that are relevant to the bio logy of other vertebrate organ systems. As examples, stem cell physiology a nd the structure of the membrane cytoskeleton were first described in hemat opoietic cells. Much of the reason for these successes resides in the ease with which blood cells can be isolated and manipulated in vitro. The cell b iology of hematopoiesis can also be illuminated by the study of human disea se states such as anemia, immunodeficiency, and leukemia. The sequential de velopment of the blood system in vertebrates is characterized by ventral me soderm induction, hematopoietic stem cell specification, and subsequent cel l lineage differentiation. Some of the key regulatory steps in this process have been uncovered by studies in mouse, chicken, and Xenopus. More recent ly, the genetics of the zebrafish (Danio rerio) have been employed to defin e novel points of regulation of the hematopoietic program. In this review, we describe the advantages of the zebrafish system for the study of blood c ell development and the initial success of the system in this pursuit. The striking similarity of zebrafish mutant phenotypes and human diseases empha sizes the utility of this model system for elucidating pathophysiologic mec hanisms. New screens for lineage-specific mutations are beginning, and the availability of transgenics promises a better understanding of lineage-spec ific gene expression. The infrastructure of the zebrafish system is growing with an NIH-directed genome initiative, providing a detailed map of the ze brafish genome and an increasing number of candidate genes for the mutation s. The zebrafish is poised to contribute greatly to our understanding of no rmal and disease-related hematopoiesis. (C) 1999 Academic Press.