{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:37:47Z","timestamp":1790001467185,"version":"4.0.1"},"reference-count":50,"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":[[2013,1,4]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Growth and remodeling of the pharyngeal arch arteries are vital for the development of a mature great vessel system. Dysmorphogenesis of the fourth arch arteries can result in interruption of the aortic arch type B, typically found in DiGeorge syndrome.\n              <jats:italic>Tbx1<\/jats:italic>\n              haploinsufficient embryos, which model DiGeorge syndrome, display fourth arch artery defects during formation of the vessels. Recovery from such defects is a documented yet unexplained phenotype in\n              <jats:italic>Tbx1<\/jats:italic>\n              haploinsufficiency.\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              To understand the nature of fourth arch artery growth recovery in\n              <jats:italic>Tbx1<\/jats:italic>\n              haploinsufficiency and its underlying genetic control.\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              We categorized vessel phenotypes of\n              <jats:italic>Tbx1<\/jats:italic>\n              heterozygotes as hypoplastic or aplastic at the conclusion of pharyngeal artery formation and compared these against the frequency of vessel defects scored at the end of great vessel development. The frequency of hypoplastic vessels decreased during embryogenesis, whereas no reduction of vessel aplasia was seen, implying recovery is attributable to remodeling of hypoplastic vessels. We showed that\n              <jats:italic>Smad7<\/jats:italic>\n              , an inhibitory Smad within the transforming growth factor-\u03b2 pathway, is regulated by Tbx1, is required for arch artery remodeling, and genetically interacts with\n              <jats:italic>Tbx1<\/jats:italic>\n              in this process.\n              <jats:italic>Tbx1<\/jats:italic>\n              and\n              <jats:italic>Tbx1<\/jats:italic>\n              ;\n              <jats:italic>Smad7<\/jats:italic>\n              haploinsufficiency affected several remodeling processes; however, concurrent haploinsufficiency particularly impacted on the earliest stage of vascular smooth muscle cell vessel coverage and subsequent fibronectin deposition. Conditional reconstitution of\n              <jats:italic>Smad7<\/jats:italic>\n              with a\n              <jats:italic>Tbx1Cre<\/jats:italic>\n              driver indicated that the interaction between the 2 genes is cell autonomous.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              <jats:italic>Tbx1<\/jats:italic>\n              acts upstream of\n              <jats:italic>Smad7<\/jats:italic>\n              controlling vascular smooth muscle and extracellular matrix investment of the fourth arch artery.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.112.270223","type":"journal-article","created":{"date-parts":[[2012,9,26]],"date-time":"2012-09-26T15:17:18Z","timestamp":1348672638000},"page":"90-102","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":50,"title":["<i>Tbx1<\/i>\n            Genetically Interacts With the Transforming Growth Factor-\u03b2\/Bone Morphogenetic Protein Inhibitor\n            <i>Smad7<\/i>\n            During Great Vessel Remodeling"],"prefix":"10.1161","volume":"112","author":[{"given":"Irinna","family":"Papangeli","sequence":"first","affiliation":[{"name":"From the Molecular Medicine Unit, UCL Institute of Child Health, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Scambler","sequence":"additional","affiliation":[{"name":"From the Molecular Medicine Unit, UCL Institute of Child Health, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.166"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20484"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.b.21182"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2005.09.006"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-009-0760-7"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-010-1607-9"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00542-4"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2002.00071.x"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600206103"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14632-6"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/511993"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/85845"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/35065105"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.028902"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.12.002"},{"key":"e_1_3_5_17_2","first-page":"3301","article-title":"Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice.","volume":"119","author":"Randall V","year":"2009","unstructured":"Randall V, McCue K, Roberts C, et al.. 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