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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3627-3636. Prepublished online as a Blood First Edition Paper on August 14, 2007; DOI 10.1182/blood-2006-04-016378. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2006-04-016378v1 110/10/3627    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bahary, N. Articles by Zon, L. I. Search for Related Content PubMed PubMed Citation Articles by Bahary, N. Articles by Zon, L. I. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish Nathan Bahary1,2, Katsutoshi Goishi3, Carsten Stuckenholz2, Gerhard Weber4, Jocelyn LeBlanc4, Christopher A. Schafer2, Sarah S. Berman2, Michael Klagsbrun3, and Leonard I. Zon4 Departments of1 Medicine and 2 Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA; 3 Vascular Biology Program, Children's Hospital, Boston, MA; and 4 The Howard Hughes Medical Institute and the Stem Cell Program and Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA Vascular endothelial growth factor A (VEGFA) and the type III receptor tyrosine kinase receptors (RTKs) are both required for the differentiation of endothelial cells (vasculogenesis) and for the sprouting of new capillaries (angiogenesis). We have isolated a duplicated zebrafish VegfA locus, termed VegfAb, and a duplicate RTK locus with homology to KDR/FLK1 (named Kdrb). Morpholino-disrupted VegfAb embryos develop a normal circulatory system until approximately 2 to 3 days after fertilization (dpf), when defects in angiogenesis permit blood to extravasate into many tissues. Unlike the VegfAa121 and VegfAa165 isoforms, the VegfAb isoforms VegfAb171 and VegfAb210 are not normally secreted when expressed in mammalian tissue culture cells. The Kdrb locus encodes a 1361–amino acid transmembrane receptor with strong homology to mammalian KDR. Combined knockdown of both RTKs leads to defects in vascular development, suggesting that they cooperate in mediating the vascular effects of VegfA in zebrafish development. Both VegfAa and VegfAb can individually bind and promote phosphorylation of both Flk1 (Kdra) and Kdrb proteins in vitro. Taken together, our data support a model in the zebrafish, in which duplicated VegfA and multiple type III RTKs mediate vascular development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. R. Swift and B. M. Weinstein Arterial-Venous Specification During Development Circ. Res., March 13, 2009; 104(5): 576 - 588. [Abstract] [Full Text] [PDF] Z.-L. Wang, X.-P. Xu, B.-L. He, S.-P. Weng, J. Xiao, L. Wang, T. Lin, X. Liu, Q. Wang, X.-Q. Yu, et al. Infectious Spleen and Kidney Necrosis Virus ORF48R Functions as a New Viral Vascular Endothelial Growth Factor J. Virol., May 1, 2008; 82(9): 4371 - 4383. [Abstract] [Full Text] [PDF]

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