Zebrafish: from hematology to hydrology.

Hemostasis is a defense mechanism that protects an organism from bleeding. Abnormal hemostasis results in bleeding disorders and thrombosis. Several factors are known to control hemostasis in mammals. Despite this progress, more factors remain to be identified. Classical genetic approaches have resolved physiological pathways. However, classical genetics could not be applied completely to hemostasis pathways a decade ago. We introduced zebrafish as a model system to study hemostasis and thrombosis using classical genetic methods. First, we established that zebrafish hemostasis is essentially similar to mammalian hemostasis. Secondly, we developed screening tools for isolating hemostatic mutants. These tools enabled us to identify hemostatic mutants, as well as providing a means to study hemostasis by knockdown methods. Continued characterization of the physiology of thrombus formation led to the novel finding of thrombocyte clustering. Recently, we have discovered that fish secrete proteases, which participate in hemostasis and may have direct relevance in humans. Future work to identify most of the players in thrombus formation is underway.