{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:07:58Z","timestamp":1793372878676,"version":"4.5.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,9,26]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Inactivating mutations in the Forkhead Box transcription factor F1 (\n                      <jats:italic>FOXF1<\/jats:italic>\n                      ) gene locus are frequently found in patients with alveolar capillary dysplasia with misalignment of pulmonary veins, a lethal congenital disorder, which is characterized by severe abnormalities in the respiratory, cardiovascular, and gastrointestinal systems. In mice, haploinsufficiency of the\n                      <jats:italic>Foxf1<\/jats:italic>\n                      gene causes alveolar capillary dysplasia and developmental defects in lung, intestinal, and gall bladder morphogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Although FOXF1 is expressed in multiple mesenchyme-derived cell types, cellular origins and molecular mechanisms of developmental abnormalities in FOXF1-deficient mice and patients with alveolar capillary dysplasia with misalignment of pulmonary veins remain uncharacterized because of lack of mouse models with cell-restricted inactivation of the\n                      <jats:italic>Foxf1<\/jats:italic>\n                      gene. In the present study, the role of FOXF1 in endothelial cells was examined using a conditional knockout approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      A novel mouse line harboring\n                      <jats:italic>Foxf1<\/jats:italic>\n                      -floxed alleles was generated by homologous recombination.\n                      <jats:italic>Tie2-Cre<\/jats:italic>\n                      and\n                      <jats:italic>Pdgfb-CreER<\/jats:italic>\n                      transgenes were used to delete\n                      <jats:italic>Foxf1<\/jats:italic>\n                      from endothelial cells. FOXF1-deficient embryos exhibited embryonic lethality, growth retardation, polyhydramnios, cardiac ventricular hypoplasia, and vascular abnormalities in the lung, placenta, yolk sac, and retina. Deletion of FOXF1 from endothelial cells reduced endothelial proliferation, increased apoptosis, inhibited vascular endothelial growth factor signaling, and decreased expression of endothelial genes critical for vascular development, including vascular endothelial growth factor receptors Flt1 and Flk1, Pdgfb, Pecam1, CD34, integrin \u03b23, ephrin B2, Tie2, and the noncoding RNA\n                      <jats:italic>Fendrr<\/jats:italic>\n                      . Chromatin immunoprecipitation assay demonstrated that Flt1, Flk1, Pdgfb, Pecam1, and Tie2 genes are direct transcriptional targets of FOXF1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>FOXF1 is required for the formation of embryonic vasculature by regulating endothelial genes critical for vascular development and vascular endothelial growth factor signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.115.304382","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T02:26:01Z","timestamp":1407205561000},"page":"709-720","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":133,"title":["FOXF1 Transcription Factor Is Required for Formation of Embryonic Vasculature by Regulating VEGF Signaling in Endothelial Cells"],"prefix":"10.1161","volume":"115","author":[{"given":"Xiaomeng","family":"Ren","sequence":"first","affiliation":[{"name":"From the Divisons of Pulmonary Biology (X.R., V.U., A.P., Y.C., J.A.H., C.S.B., J.M.S., T.V.K., V.V.K.) and Developmental Biology (V.V.K.), Perinatal Institute, Cincinnati Children\u2019s Research Foundation, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Ustiyan","sequence":"additional","affiliation":[{"name":"From the Divisons of Pulmonary Biology (X.R., V.U., A.P., Y.C., J.A.H., C.S.B., J.M.S., T.V.K., V.V.K.) and Developmental Biology (V.V.K.), Perinatal Institute, Cincinnati Children\u2019s Research Foundation, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Pradhan","sequence":"additional","affiliation":[{"name":"From the Divisons of Pulmonary Biology (X.R., V.U., A.P., Y.C., J.A.H., C.S.B., J.M.S., T.V.K., V.V.K.) and Developmental Biology (V.V.K.), Perinatal Institute, Cincinnati Children\u2019s Research Foundation, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Cai","sequence":"additional","affiliation":[{"name":"From the Divisons of Pulmonary Biology (X.R., V.U., A.P., Y.C., J.A.H., C.S.B., J.M.S., T.V.K., V.V.K.) and Developmental Biology (V.V.K.), Perinatal Institute, Cincinnati Children\u2019s Research Foundation, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie A.","family":"Havrilak","sequence":"additional","affiliation":[{"name":"From the Divisons of Pulmonary Biology (X.R., V.U., A.P., Y.C., J.A.H., C.S.B., J.M.S., T.V.K., V.V.K.) and Developmental Biology (V.V.K.), Perinatal Institute, Cincinnati Children\u2019s Research Foundation, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig S.","family":"Bolte","sequence":"additional","affiliation":[{"name":"From the Divisons of Pulmonary Biology (X.R., V.U., A.P., Y.C., J.A.H., C.S.B., J.M.S., T.V.K., V.V.K.) and Developmental Biology (V.V.K.), Perinatal Institute, Cincinnati Children\u2019s Research Foundation, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Shannon","sequence":"additional","affiliation":[{"name":"From the Divisons of Pulmonary Biology (X.R., V.U., A.P., Y.C., J.A.H., C.S.B., J.M.S., T.V.K., V.V.K.) and Developmental Biology (V.V.K.), Perinatal Institute, Cincinnati Children\u2019s Research Foundation, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya V.","family":"Kalin","sequence":"additional","affiliation":[{"name":"From the Divisons of Pulmonary Biology (X.R., V.U., A.P., Y.C., J.A.H., C.S.B., J.M.S., T.V.K., V.V.K.) and Developmental Biology (V.V.K.), Perinatal Institute, Cincinnati Children\u2019s Research Foundation, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir 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