{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:11:43Z","timestamp":1789182703240,"version":"build-2803163510"},"reference-count":70,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,1,6]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Positive signals, such as vascular endothelial growth factor, direct endothelial cells (ECs) to specific locations during blood vessel formation. Less is known about repulsive signal contribution to shaping vessels. Recently, \u201cneuronal guidance cues\u201d have been shown to influence EC behavior, particularly in directing sprouting angiogenesis by repelling ECs. However, their role during de novo blood vessel formation remains unexplored.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To identify signals that guide and pattern the first mammalian blood vessels.<\/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              Using genetic mouse models, we show that blood vessels are sculpted through the generation of stereotyped avascular zones by EC-repulsive cues. We demonstrate that Semaphorin3E (Sema3E) is a key factor that shapes the paired dorsal aortae in mouse, as\n              <jats:italic>sema3E<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              embryos develop an abnormally branched aortic plexus with a markedly narrowed avascular midline. In vitro cultures and avian grafting experiments show strong repulsion of ECs by Sema3E-expressing cells. We further identify the mouse notochord as a rich source of multiple redundant neuronal guidance cues. Mouse embryos that lack notochords fail to form cohesive aortic vessels because of loss of the avascular midline, yet maintain lateral avascular zones. We demonstrate that lateral avascular zones are directly generated by the lateral plate mesoderm, a critical source of Sema3E.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>These findings demonstrate that Sema3E-generated avascular zones are critical regulators of mammalian cardiovascular patterning and are the first to identify a repulsive role for the lateral plate mesoderm. Integration of multiple, and in some cases redundant, repulsive cues from various tissues is critical to patterning the first embryonic blood vessels.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.111.249847","type":"journal-article","created":{"date-parts":[[2011,11,11]],"date-time":"2011-11-11T02:59:02Z","timestamp":1320980342000},"page":"34-46","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Integration of Repulsive Guidance Cues Generates Avascular Zones That Shape Mammalian Blood Vessels"],"prefix":"10.1161","volume":"110","author":[{"given":"Stryder M.","family":"Meadows","sequence":"first","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Moran","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gera","family":"Neufeld","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Chauvet","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Mann","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Krieg","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondine","family":"Cleaver","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX (S.M.M., P.J.F., K.X., O.C.); the Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ (C.M., P.K.); Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel (G.N.); and Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00757-2"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001875"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01039"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-07-04738.1995"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1305405"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.06.008"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.09.013"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03875"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5290.1123"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81436-1"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.2.269"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03080"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408318102"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00516"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105416"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.06.002"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.8495"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00127-3"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.02.010"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.02.033"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609711200"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01304"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.5.1671.005k39_1671_1679"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(91)90316-U"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-1970"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.883901"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.881501"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90522-3"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.14.2533"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.10.012"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.0106"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.08.011"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2005.01.008"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1402510210"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003287"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.19.3905"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.10.045"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01652-09"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00258-6"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1742"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000678"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001896107"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.12.001"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405984101"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.17.6624"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.11.5026"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12643.x"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.55"},{"key":"e_1_3_5_50_2","first-page":"1138","article-title":"Chordin-like 1, a bone morphogenetic protein-4 antagonist, is upregulated by hypoxia in human retinal pericytes and plays a role in regulating angiogenesis","volume":"14","author":"Kane R","year":"2008","unstructured":"Kane R, Godson C, O'Brien C. 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