The role of meis1 in primitive and definitive haematopoiesis during zebrafish development

Background. The Meis1 protein represents an important cofactor for Hox and Pbx1 and is implicated in human and murine leukaemias. Though much is known about the role of meis1 in leukaemogenesis, its function in normal haematopoiesis, remains largely unclear. Here we characterise the role of the proto-oncogene, meis1, during zebrafish primitive and definitive hematopoiesis. Design and Methods. Using antisense morpholino oligonucleotides to interrupt meis1 expression we find that, although primitive macrophage development can occur unhampered, the posterior erythroid differentiation requires meis1, resulting in severe decrease in number of mature erythrocytes. Furthermore a picture emerges that meis1 exerts important effects on later stages of erythrocyte maturation and these effects are independent of gata1, but under the control of scl. Results. In addition, meis1 morpholino knock-down leads to dramatic single arteriovenous tube formation. We also find that knock-down of pbx1 results in a strikingly similar phenotype to that of meis1 knock-down. Conclusion. Thus, these results implicate that meis1, jointly with pbx1, regulates primitive haematopoiesis as well as vascular development.