The main aim of the present project is to provide the first description of embryonic megakaryocyte function during vascular development and maintenance. The recent description of embryonic megakaryocytes existence together with the presence of vascular defects in all mouse mutant models that lack embryonic megakaryocytes suggests that a cellular interaction between embryonic megakaryocytes and endothelium is essential for the correct patterning and stability of the vasculature. The vascular system is the first organ to become functional in the embryo and its regulatory mechanisms are of ultimate medical importance in cancer, development, homeostasis, healing and regeneration. Likewise, blood and endothelium develop in close association and it is surprising to realize how little we know on how specific haematopoietic lineages support the development of a functional vasculature. We will address this important issue by characterizing the function of Meis1 in the megakaryocytic lineage and of the megakaryocytic lineage in vascularization. Meis1 mutant mice are the only known mutant mice that lack embryonic megakaryocytes without another apparent haematopoietic deficiency. Therefore, Meis1 null mice present a unique opportunity to investigate this common denominator – absence of megakaryocytes – on all haematopoietic mutants that present vascular defects. We will achieve this goal by: 1) a detailed characterization of the Meis1 vascular defect using histological approaches and optical projection tomography; 2) imaging the behaviour and interaction of the megakaryocyte cellular equivalents and the endothelium in live zebrafish embryos; and 3) establish the role of Meis1 and of embryonic megakaryocytes in embryonic vascularization through the targeted elimination of this lineage, the rescue of Meis1 null vascular phenotype by megakaryocyte progenitor transplantation and by the conditional reactivation of Meis function in the megakaryocytic lineage of Meis1 null embryos.