title: Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo.
abstract: Although many of the cellular and molecular mechanisms of angiogenesis have been intensely studied [1], little is known about the processes that underlie vascular anastomosis. We have generated transgenic fish lines expressing an EGFP-tagged version of the junctional protein zona occludens 1 (ZO1) to visualize individual cell behaviors that occur during vessel fusion and lumen formation in vivo. These life observations show that endothelial cells (ECs) use two distinct morphogenetic mechanisms, cell membrane invagination and cord hollowing to generate different types of vascular tubes. During initial steps of anastomosis, cell junctions that have formed at the initial site of cell contacts expand into rings, generating a cellular interface of apical membrane compartments, as defined by the localization of the apical marker podocalyxin-2 (Pdxl2). During the cord hollowing process, these apical membrane compartments are brought together via cell rearrangements and extensive junctional remodeling, resulting in lumen coalescence and formation of a multicellular tube. Vessel fusion by membrane invagination occurs adjacent to a preexisting lumen in a proximal to distal direction and is blood-flow dependent. Here, the invaginating inner cell membrane undergoes concomitant apicobasal polarization and the vascular lumen is formed by the extension of a transcellular lumen through the EC, which forms a unicellular or seamless tube.
authors.affiliation: Biozentrum der Universität Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Herwig
authors.forename: Yannick
authors.initials: Y
authors.lastname: Blum
authors.forename: Alice
authors.initials: A
authors.lastname: Krudewig
authors.forename: Elin
authors.initials: E
authors.lastname: Ellertsdottir
authors.forename: Anna
authors.initials: A
authors.lastname: Lenard
authors.forename: Heinz-Georg
authors.initials: HG
authors.lastname: Belting
authors.forename: Markus
authors.initials: M
authors.lastname: Affolter
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D001808:Blood Vessels / Q000033:anatomy & histology / Q000196:embryology*; D002462:Cell Membrane / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000196:embryology; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D007365:Intercellular Junctions / Q000235:genetics / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009024:Morphogenesis; D010750:Phosphoproteins / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics; D062826:Zonula Occludens-1 Protein
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D062826:Zonula Occludens-1 Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins