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The role of KLF4, and the possible overlapping functions of KLF2 and KLF4, in the developing vasculature are not well-studied.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Endothelial breaks are observed in a major vessel, the primary head vein (PHV), in KLF2-\/-KLF4-\/- embryos at E9.5. KLF2-\/-KLF4-\/- embryos die by E10.5, which is earlier than either single knockout. Gross hemorrhaging of multiple vessels may be the cause of death. E9.5 KLF2-\/-KLF4+\/- embryos do not exhibit gross hemorrhaging, but cross-sections display disruptions of the endothelial cell layer of the PHV, and these embryos generally also die by E10.5. Electron micrographs confirm that there are gaps in the PHV endothelial layer in E9.5 KLF2-\/-KLF4-\/- embryos, and show that the endothelial cells are abnormally bulbous compared to KLF2-\/- and wild-type (WT). The amount of endothelial Nitric Oxide Synthase (eNOS) mRNA, which encodes an endothelial regulator, is reduced by 10-fold in E9.5 KLF2-\/-KLF4-\/- compared to KLF2-\/- and WT embryos. VEGFR2, an eNOS inducer, and occludin, a tight junction protein, gene expression are also reduced in E9.5 KLF2-\/-KLF4-\/- compared to KLF2-\/- and WT embryos.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This study begins to define the roles of KLF2 and KLF4 in the embryonic development of blood vessels. It indicates that the two genes interact to maintain an intact endothelial layer. KLF2 and KLF4 positively regulate the eNOS, VEGFR2 and occludin genes. Down-regulation of these genes in KLF2-\/-KLF4-\/- embryos may result in the observed loss of vascular integrity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-213x-13-40","type":"journal-article","created":{"date-parts":[[2013,11,22]],"date-time":"2013-11-22T02:02:09Z","timestamp":1385085729000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["The Kr\u00fcppel-like factor 2 and Kr\u00fcppel-like factor 4 genes interact to maintain endothelial integrity in mouse embryonic vasculogenesis"],"prefix":"10.1186","volume":"13","author":[{"given":"Aditi R","family":"Chiplunkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin C","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel L","family":"Eades","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan S","family":"Kane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean J","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack L","family":"Haar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce A","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,11,22]]},"reference":[{"key":"751_CR1","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1146\/annurev.cellbio.18.012502.105825","volume":"18","author":"J Rossant","year":"2002","unstructured":"Rossant J, Howard L: Signaling pathways in vascular development. 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