title: Venous-derived angioblasts generate organ-specific vessels during zebrafish embryonic development.
abstract: Formation and remodeling of vascular beds are complex processes orchestrated by multiple signaling pathways. Although 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 and 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 in which 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 forms and expands ventrally through a Bone Morphogenetic Protein-dependent step of collective migration. Concomitantly, a Vascular Endothelial Growth Factor-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. Together, 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.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Gideon
authors.initials: G
authors.lastname: Hen
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Julian
authors.initials: J
authors.lastname: Nicenboim
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Mayseless
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Lihee
authors.initials: L
authors.lastname: Asaf
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shin
authors.affiliation: Department of Biology, University of Padova, Padova I-35131, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Busolin
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Roy
authors.initials: R
authors.lastname: Hofi
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Almog
authors.affiliation: Department of Biology, University of Padova, Padova I-35131, Italy.
authors.forename: Natascia
authors.initials: N
authors.lastname: Tiso
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Lawson
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel karina.yaniv@weizmann.ac.il.
authors.forename: Karina
authors.initials: K
authors.lastname: Yaniv
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology; D002465:Cell Movement; D004064:Digestive System / Q000098:blood supply; D047108:Embryonic Development; D042783:Endothelial Cells / Q000166:cytology; D008099:Liver / Q000098:blood supply; D009928:Organ Specificity; D051880:Receptors, Notch / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism; D014680:Veins / Q000166:cytology* / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D051880:Receptors, Notch
keywords: Angioblast; Angiogenesis; Zebrafish