title: Vegfc is required for vascular development and endoderm morphogenesis in zebrafish.
abstract: During embryogenesis, complex morphogenetic events lead endodermal cells to coalesce at the midline and form the primitive gut tube and associated organs. While several genes have recently been implicated in endoderm differentiation, we know little about the genes that regulate endodermal morphogenesis. Here, we show that vascular endothelial growth factor C (Vegfc), an angiogenic as well as a lymphangiogenic factor, is unexpectedly involved in this process in zebrafish. Reducing Vegfc levels using morpholino antisense oligonucleotides, or through overexpression of a soluble form of the VEGFC receptor, VEGFR-3, affects the coalescence of endodermal cells in the anterior midline, leading to the formation of a forked gut tube and the duplication of the liver and pancreatic buds. Further analyses indicate that Vegfc is additionally required for the initial formation of the dorsal endoderm. We also demonstrate that Vegfc is required for vasculogenesis as well as angiogenesis in the zebrafish embryo. These data argue for a requirement of Vegfc in the developing vasculature and, more surprisingly, implicate Vegfc signalling in two distinct steps during endoderm development, first during the initial differentiation of the dorsal endoderm, and second in the coalescence of the anterior endoderm to the midline.
authors.affiliation: Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, California 94143-0448, USA.
authors.forename: Elke A
authors.initials: EA
authors.lastname: Ober
authors.forename: Birgitta
authors.initials: B
authors.lastname: Olofsson
authors.forename: Taija
authors.initials: T
authors.lastname: Mäkinen
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Jin
authors.forename: Wataru
authors.initials: W
authors.lastname: Shoji
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D004707:Endoderm / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009024:Morphogenesis; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D042582:Vascular Endothelial Growth Factor C; D029961:Zebrafish Proteins; C493178:vascular endothelial growth factor C, zebrafish