SEARCH:   Advanced

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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 12, 2006 Accepted July 11, 2007 Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish Nathan Bahary*, Katsutoshi Goishi, Carsten Stuckenholz, Gerhard Weber, Jocelyn LeBlanc, Christopher A Schafer, Sarah S Berman, Michael Klagsbrun, and Leonard I Zon Department of Medicine, Division of Oncology, University of Pittsburgh, Pittsburgh, PA, United States Vascular Biology Program, Children's Hospital, Boston, MA, United States Dept of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA, United States HHMI & Stem Cell Program & Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA, United States * Corresponding author; email: bahary{at}pitt.edu. 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 2-3 dpf, when defects in angiogenesis permits 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 phosporylation 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: B. M. Hogan, R. Herpers, M. Witte, H. Helotera, K. Alitalo, H. J. Duckers, and S. Schulte-Merker Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries Development, December 1, 2009; 136(23): 4001 - 4009. [Abstract] [Full Text] [PDF] 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]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020