{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:39:49Z","timestamp":1792690789338,"version":"4.5.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2014,6,4]],"date-time":"2014-06-04T00:00:00Z","timestamp":1401840000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0098646","type":"journal-article","created":{"date-parts":[[2014,6,4]],"date-time":"2014-06-04T20:28:44Z","timestamp":1401913724000},"page":"e98646","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":145,"title":["Endothelial Depletion of Acvrl1 in Mice Leads to Arteriovenous Malformations Associated with Reduced Endoglin Expression"],"prefix":"10.1371","volume":"9","author":[{"given":"Simon","family":"Tual-Chalot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen R.","family":"Allinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael E.","family":"Redgrave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Paul","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Fruttiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Arthur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,6,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1073\/pnas.97.6.2626","article-title":"Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis","volume":"97","author":"SP Oh","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1182\/blood-2006-07-034124","article-title":"Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells","volume":"109","author":"L David","year":"2007","journal-title":"Blood"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1161\/CIRCRESAHA.107.165530","article-title":"Bone Morphogenetic Protein-9 Is a Circulating Vascular Quiescence Factor","volume":"102","author":"L David","year":"2008","journal-title":"Circ Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1242\/jcs.002949","article-title":"BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis","volume":"120","author":"M Scharpfenecker","year":"2007","journal-title":"J Cell Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng0696-189","article-title":"Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2","volume":"13","author":"DW Johnson","year":"1996","journal-title":"Nat Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.blre.2010.07.001","article-title":"Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment","volume":"24","author":"CL Shovlin","year":"2010","journal-title":"Blood Rev"},{"key":"ref7","first-page":"3487","article-title":"Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia","volume":"119","author":"SO Park","year":"2009","journal-title":"J Clin Invest"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1161\/STROKEAHA.113.003655","article-title":"De novo cerebrovascular malformation in the adult mouse after endothelial Alk1 deletion and angiogenic stimulation","volume":"45","author":"W Chen","year":"2014","journal-title":"Stroke"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1242\/dev.129.12.3009","article-title":"Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels","volume":"129","author":"BL Roman","year":"2002","journal-title":"Development"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1242\/dev.060467","article-title":"Interaction between alk1 and blood flow in the development of arteriovenous malformations","volume":"138","author":"P Corti","year":"2011","journal-title":"Development"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.devcel.2012.02.005","article-title":"ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway","volume":"22","author":"B Larrivee","year":"2012","journal-title":"Dev Cell"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1161\/CIRCRESAHA.109.211037","article-title":"Pathogenesis of arteriovenous malformations in the absence of endoglin","volume":"106","author":"M Mahmoud","year":"2010","journal-title":"Circ Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature09002","article-title":"Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis","volume":"465","author":"Y Wang","year":"2010","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1182\/blood-2007-08-107359","article-title":"ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2","volume":"111","author":"SO Park","year":"2008","journal-title":"Blood"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nm.2131","article-title":"Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia","volume":"16","author":"F Lebrin","year":"2010","journal-title":"Nat Med"},{"key":"ref16","first-page":"e50546","article-title":"Whole mount immunofluorescent staining of the neonatal mouse retina to investigate angiogenesis in vivo. J Vis Exp","volume":"77","author":"S Tual-Chalot","year":"2013"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/nprot.2010.113","article-title":"Inducible gene targeting in the neonatal vasculature and analysis of retinal angiogenesis in mice","volume":"5","author":"ME Pitulescu","year":"2010","journal-title":"Nat Protoc"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e39336","DOI":"10.1371\/journal.pone.0039336","article-title":"Endothelial expression of TGFbeta type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system","volume":"7","author":"KR Allinson","year":"2012","journal-title":"PLoS One"},{"key":"ref19","first-page":"e2316","article-title":"Isolation and culture of pulmonary endothelial cells from neonatal mice. J Vis Exp","volume":"46","author":"M Sobczak","year":"2010"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s10456-007-9065-1","article-title":"Development of the retinal vasculature","volume":"10","author":"M Fruttiger","year":"2007","journal-title":"Angiogenesis"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cardiores.2005.06.009","article-title":"Blood outgrowth endothelial cells from Hereditary Haemorrhagic Telangiectasia patients reveal abnormalities compatible with vascular lesions","volume":"68","author":"LA Fernandez","year":"2005","journal-title":"Cardiovasc Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"8712","DOI":"10.1093\/nar\/gkr572","article-title":"ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif","volume":"39","author":"M Morikawa","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1182\/blood-2012-07-440784","article-title":"BMP9 regulates endoglin-dependent chemokine responses in endothelial cells","volume":"120","author":"K Young","year":"2012","journal-title":"Blood"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"15794","DOI":"10.1074\/jbc.M109.002881","article-title":"Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells","volume":"284","author":"PD Upton","year":"2009","journal-title":"J Biol Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nature05571","article-title":"Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis","volume":"445","author":"M Hellstrom","year":"2007","journal-title":"Nature"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1242\/dev.063933","article-title":"Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo","volume":"138","author":"J Krueger","year":"2011","journal-title":"Development"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ydbio.2006.03.035","article-title":"The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development","volume":"294","author":"S Seo","year":"2006","journal-title":"Dev Biol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2009.07.047","article-title":"Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization","volume":"139","author":"X Ye","year":"2009","journal-title":"Cell"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"6162","DOI":"10.1182\/blood-2012-01-407593","article-title":"BMP9 and BMP10 are critical for postnatal retinal vascular remodeling","volume":"119","author":"N Ricard","year":"2012","journal-title":"Blood"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.devcel.2012.01.007","article-title":"Stalk cell phenotype depends on integration of Notch and Smad1\/5 signaling cascades","volume":"22","author":"IM Moya","year":"2012","journal-title":"Dev Cell"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/sj.emboj.7600065","article-title":"Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells","volume":"23","author":"F Itoh","year":"2004","journal-title":"EMBO J"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1101\/gad.1239204","article-title":"Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants","volume":"18","author":"LT Krebs","year":"2004","journal-title":"Genes Dev"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/dvg.20599","article-title":"Notch1 activation in mice causes arteriovenous malformations phenocopied by ephrinB2 and EphB4 mutants","volume":"48","author":"LT Krebs","year":"2010","journal-title":"Genesis"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"117ra8","DOI":"10.1126\/scitranslmed.3002670","article-title":"Notch4 normalization reduces blood vessel size in arteriovenous malformations","volume":"4","author":"PA Murphy","year":"2012","journal-title":"Sci Transl Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/81634","article-title":"Arteriovenous malformations in mice lacking activin receptor-like kinase-1","volume":"26","author":"LD Urness","year":"2000","journal-title":"Nat Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ng1294-345","article-title":"Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1","volume":"8","author":"KA McAllister","year":"1994","journal-title":"Nat Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/0002-9394(89)90261-4","article-title":"Ocular manifestations in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease)","volume":"107","author":"AM Brant","year":"1989","journal-title":"Am J Ophthalmol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1111\/j.1755-3768.1979.tb00541.x","article-title":"Ocular lesions in hereditary haemorrhagic telangiectasia","volume":"57","author":"I Vase","year":"1979","journal-title":"Acta Ophthalmol (Copenh)"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"30034","DOI":"10.1074\/jbc.M111.260133","article-title":"Soluble Endoglin Specifically Binds Bone Morphogenetic Proteins 9 and 10 via Its Orphan Domain, Inhibits Blood Vessel Formation, and Suppresses Tumor Growth","volume":"286","author":"R Castonguay","year":"2011","journal-title":"J Biol Chem"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e29948","DOI":"10.1371\/journal.pone.0029948","article-title":"Structural and functional insights into endoglin ligand recognition and binding","volume":"7","author":"A Alt","year":"2012","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"4018","DOI":"10.1038\/sj.emboj.7600386","article-title":"Endoglin promotes endothelial cell proliferation and TGF-beta\/ALK1 signal transduction","volume":"23","author":"F Lebrin","year":"2004","journal-title":"Embo J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1373\/clinchem.2004.035287","article-title":"Mutation analysis in Spanish patients with hereditary hemorrhagic telangiectasia: deficient endoglin up-regulation in activated monocytes","volume":"50","author":"F Sanz-Rodriguez","year":"2004","journal-title":"Clin Chem"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1093\/hmg\/9.8.1227","article-title":"Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2","volume":"9","author":"SA Abdalla","year":"2000","journal-title":"Hum Mol Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1182\/blood-2009-07-235655","article-title":"ALK1 signaling regulates early postnatal lymphatic vessel development","volume":"115","author":"K Niessen","year":"2010","journal-title":"Blood"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1182\/blood-2012-12-472142","article-title":"Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation","volume":"122","author":"S Levet","year":"2013","journal-title":"Blood"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1096\/fj.03-0197fje","article-title":"Endoglin regulates nitric oxide-dependent vasodilatation","volume":"18","author":"M Jerkic","year":"2004","journal-title":"FASEB J"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/labinvest.2008.112","article-title":"Endoglin and Activin Receptor-Like-Kinase 1 are Co-expressed in the Distal Vessels of the Lung","volume":"89","author":"M Mahmoud","year":"2009","journal-title":"Lab Invest"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1161\/ATVBAHA.112.300485","article-title":"Reduced Mural Cell Coverage and Impaired Vessel Integrity After Angiogenic Stimulation in the Alk1-deficient Brain","volume":"33","author":"W Chen","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1148\/rg.281075037","article-title":"Abdominal findings in hereditary hemorrhagic telangiectasia: pictorial essay on 2D and 3D findings with isotropic multiphase CT","volume":"28","author":"H Siddiki","year":"2008","journal-title":"Radiographics"},{"key":"ref50","first-page":"728","article-title":"Hereditary hemorrhagic telangiectasia","volume":"90","author":"J McDonald","year":"2005","journal-title":"Haematologica"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1016\/j.bbadis.2013.05.016","article-title":"The ALK-1\/Smad1 pathway in cardiovascular physiopathology. A new target for therapy?","volume":"1832","author":"M Gonzalez-Nunez","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1084\/jem.20091309","article-title":"Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis","volume":"207","author":"SI Cunha","year":"2010","journal-title":"J Exp Med"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"a006452","DOI":"10.1101\/cshperspect.a006452","article-title":"VEGF-directed blood vessel patterning: from cells to organism","volume":"2","author":"VL Bautch","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/ni1013","article-title":"Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins","volume":"5","author":"MJ Karkkainen","year":"2004","journal-title":"Nat Immunol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0098646","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T09:18:34Z","timestamp":1716801514000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0098646"}},"subtitle":[],"editor":[{"given":"Vesa","family":"Kaartinen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,6,4]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2014,6,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0098646","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,4]]}}}