The development of mammalian megakaryocytes (MKs) and platelets, which are thought to be absent in non-mammals, is primarily regulated by the thrombopoietin (TPO)/Mpl system. Although non-mammals possess nucleated thrombocytes instead of platelets, the features of nucleated thrombocyte progenitors remain to be clarified. Here, we provide the general features of TPO using Xenopus laevis TPO (xlTPO). Platelets are generated from the cytoplasm of polyploid megakaryocytes (MKs). In humans, MKs differentiate from haematopoietic stem cells (HSCs) and constitute only a small fraction of bone marrow cells (0.1%-0.5%) 1 . MKs are unique cells that undergo DNA replication, giving rise to polyploid cells that undergo proplatelet formation 2 . The proliferation and maturation of MKs by thrombopoietin (TPO), a ligand for the receptor encoded by the c-mpl proto-oncogene (Mpl) 3-5 , has been well characterized. TPO has been independently identified and purified from different species in mammals 6,7 . In contrast, the origin and development of circulating nucleated thrombocytes in most non-mammalian vertebrates, including fish 8-10 , amphibians 11 , reptiles 12 and aves 13 , remain unknown 14,15 . The evolutionary advantage of deriving platelets from MKs has been previously discussed 16 . Circulating thrombocytes mediate haemostasis and blood coagulation, and result in the activation and cytoskeletal changes of non-mammalian nucleated thrombocytes, similar to those of platelets 17 . In zebrafish, thrombin activates nucleated thrombocytes produced by TPO stimulation 18 . Nevertheless, it is not clear whether polyploid MKs are the precursors of mature nucleate thrombocytes.In humans, HSCs develop into committed multipotent progenitors, which in turn differentiate to produce lymphocyte progenitors, granulocyte/monocyte progenitors, and MK/erythroid progenitors (MEPs). MEPs committed to the formation of erythroid and megakaryocytic progeny then produce mature erythrocytes or platelets 19 . Although TPO is one of the most important inducers of MK maturation, high concentrations of TPO inhibit proplatelet formation in vitro 20 . Recently, Nishimura et al. reported that the IL-1α also stimulates platelet production in response to acute platelet needs 21 . Newly released peripheral platelets exhibit bipolar morphology of round cells and multi-bodied proplatelets 22 . Proplatelet formation and platelet release are accelerated by shear forces in vitro 23 .