title: Molecular basis for Flk1 expression in hemato-cardiovascular progenitors in the mouse.
abstract: The mouse Flk1 gene is expressed in various mesodermal progenitor cells of developing embryos. Recent studies have shown that Flk1 expression marks multipotent mesodermal progenitors, giving rise to various hemato-cardiovascular cell lineages during development. Flk1 expression also marks hemato-cardiovascular cell lineages in differentiating embryonic stem (ES) cells, which may be used in transplantation decisions to treat cardiovascular diseases. Despite its developmental and clinical importance in cardiovascular tissues, the transcriptional regulatory system of Flk1 has remained unclear. Here, we report a novel enhancer of the mouse Flk1 gene directing early mesodermal expression during development as well as ES differentiation. The enhancer enriches various mesodermal progenitors, such as primitive erythropoietic progenitors, hemangioblast (BL-CFC) and cardiovascular progenitors (CV-CFC). The enhancer is activated by Bmp, Wnt and Fgf, and it contains Gata-, Cdx-, Tcf/Lef-, ER71/Etv2- and Fox-binding sites, some of which are bound specifically by each of these transcription factors. As these transcription factors are known to act under the control of the Bmp, Wnt and Fgf families, early Flk1 expression may be induced by cooperative interactions between Gata, Tcf/Lef, Cdx and ER71/Etv2 under the control of Bmp, Wnt and Fgf signaling. The enhancer is required for early Flk1 expression and for hemangioblast development during ES differentiation.
authors: Department of Anatomy and Embryology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai,Tsukuba, Ibaraki, Japan.
authors: Hiroyuki
authors: H
authors: Ishitobi
authors: Asami
authors: A
authors: Wakamatsu
authors: Fang
authors: F
authors: Liu
authors: Takuya
authors: T
authors: Azami
authors: Michito
authors: M
authors: Hamada
authors: Ken
authors: K
authors: Matsumoto
authors: Hiroshi
authors: H
authors: Kataoka
authors: Makoto
authors: M
authors: Kobayashi
authors: Kyunghee
authors: K
authors: Choi
authors: Shin-ichi
authors: S
authors: Nishikawa
authors: Satoru
authors: S
authors: Takahashi
authors: Masatsugu
authors: M
authors: Ema
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000201:enzymology* / Q000254:growth & development*; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000201:enzymology*; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D008648:Mesoderm / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D014157:Transcription Factors / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D040301:Vascular Endothelial Growth Factor Receptor-2