Venous-derived angioblasts generate organ-specific vessels during embryonic development

Abstract

Formation and remodeling of vascular beds are complex processes orchestrated by multiple signaling pathways. While it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions, the embryonic origins of tissue-specific vessels, as well as the molecular mechanisms regulating their formation, are poorly understood. The subintestinal plexus of the zebrafish embryo comprises vessels that vascularize the gut, liver and pancreas, and as such represents an ideal model to investigate the early steps of organ-specific vessel formation. Here we show that both arterial and venous components of the subintestinal plexus originate from a pool of specialized angioblasts residing in the floor of the Posterior Cardinal Vein (PCV). Using live imaging of zebrafish embryos, in combination with photoconvertable transgenic reporters, we demonstrate that these angioblasts undergo two phases of migration and differentiation. Initially, a subintestinal vein (SIV) forms and expands ventrally through a bone morphogenetic protein (BMP)-dependent step of collective migration. Concomitantly, a VEGF-dependent shift in the directionality of migration, coupled to the upregulation of arterial markers is observed, which culminates with the generation of the supraintestinal artery (SIA). Altogether our results establish the zebrafish subintestinal plexus as an advantageous model for the study of organ-specific vessel development, and provide new insights into the molecular mechanisms controlling its formation. More broadly, our findings suggest that PCV-specialized angioblasts contribute not only to the formation of the early trunk vasculature, but also to the establishment of late forming-, tissue specific vascular beds.