title: The LIM-homeodomain transcription factor Islet2a promotes angioblast migration.
abstract: Angioblasts of the developing vascular system require many signaling inputs to initiate their migration, proliferation and differentiation into endothelial cells. What is less studied is which intrinsic cell factors interpret these extrinsic signals. Here, we show the Lim homeodomain transcription factor islet2a (isl2a) is expressed in the lateral posterior mesoderm prior to angioblast migration. isl2a deficient angioblasts show disorganized migration to the midline to form axial vessels and fail to spread around the tailbud of the embryo. Isl2a morphants have fewer vein cells and decreased vein marker expression. We demonstrate that isl2a is required cell autonomously in angioblasts to promote their incorporation into the vein, and is permissive for vein identity. Knockout of isl2a results in decreased migration and proliferation of angioblasts during intersegmental artery growth. Since Notch signaling controls both artery-vein identity and tip-stalk cell formation, we explored the interaction of isl2a and Notch. We find that isl2a expression is negatively regulated by Notch activity, and that isl2a positively regulates flt4, a VEGF-C receptor repressed by Notch during angiogenesis. Thus Isl2a may act as an intermediate between Notch signaling and genetic programs controlling angioblast number and migration, placing it as a novel transcriptional regulator of early angiogenesis.
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Lamont
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1.
authors.forename: Jae-Ryeon
authors.initials: JR
authors.lastname: Ryu
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1.
authors.forename: Wendy
authors.initials: W
authors.lastname: Vu
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1.
authors.forename: Paniz
authors.initials: P
authors.lastname: Davari
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Sobering
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1.
authors.forename: Regan M
authors.initials: RM
authors.lastname: Kennedy
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Munsie
authors.affiliation: Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary AB, Canada, T2N 4N1. Electronic address: schilds@ucalgary.ca.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Childs
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001158:Arteries / Q000196:embryology; D002465:Cell Movement; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D060850:LIM-Homeodomain Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm; D060172:Morpholinos / Q000235:genetics / Q000633:toxicity; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051880:Receptors, Notch / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000502:physiology; D014680:Veins / Q000196:embryology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C000621727:fli1 protein, zebrafish; D060850:LIM-Homeodomain Proteins; D060172:Morpholinos; D012333:RNA, Messenger; D051880:Receptors, Notch; D014157:Transcription Factors; D029961:Zebrafish Proteins; C490404:isl2a protein, zebrafish; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Angioblast; Artery; Islet2a; Notch; Vein