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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4536-4544. Prepublished online as a Blood First Edition Paper on February 24, 2004; DOI 10.1182/blood-2003-11-3827. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: 2003-11-3827v1 103/12/4536    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 Zippo, A. Articles by Oliviero, S. Search for Related Content PubMed PubMed Citation Articles by Zippo, A. Articles by Oliviero, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted November 12, 2003 Accepted February 11, 2004 Identification of Flk-1-target genes in vasculogenesis: Pim-1 is required for endothelial and mural cell differentiation in vitro Alessio Zippo, Alessandra De Robertis, Monia Bardelli, Federico Galvagni, and Salvatore Oliviero* Biologia Molecolare, University of Siena, Siena, Italy * Corresponding author; email: oliviero{at}unisi.it. The tyrosine kinase receptor Fetal liver kinase (Flk)-1 plays a crucial role in vasculogenesis and angiogenesis, but its target genes remains elusive. Comparing Flk-1 +/+ with Flk-1 -/- ES cells we identified transcripts regulated by the VEGF-A / Flk-1 pathway at an early stage of their differentiation to endothelial and mural precursors. Further analysis of a number of these genes (Nm23-M1, Nm23-M2, Slug, Set, pp32, Cbp, Ship-1, Btk, and Pim-1) showed that their products were transiently up-regulated in vivo in endothelial cells (EC) during angiogenesis of the ovary and their mRNA were rapidly induced in vitro by VEGF-A in human umbilical cord vein endothelial cells (HUVEC). Functional analysis by RNA interference (RNAi) in ES induced to differentiate demonstrated that Pim-1 is required for their differentiation into EC and smooth muscle cells (SMC). In HUVEC RNAi showed that Pim-1 is required in EC for VEGF-A-dependent proliferation and migration. The identification of Flk-1 target genes should help in elucidating the molecular pathways that govern the vasculogenesis and angiogenesis processes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: VEGF receptors branch into new areas Steven A. Stacker and Marc G. Achen Blood 2004 103: 4379-4380. 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