{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T23:28:35Z","timestamp":1783812515422,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T00:00:00Z","timestamp":1463616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/12\/44\/29619"],"award-info":[{"award-number":["FS\/12\/44\/29619"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The heart is the first functioning organ to develop during embryogenesis. The formation of the heart is a tightly regulated and complex process, and alterations to its development can result in congenital heart defects. Mutations in sarcomeric proteins, such as alpha myosin heavy chain and cardiac alpha actin, have now been associated with congenital heart defects in humans, often with atrial septal defects. However, cardiac troponin T (<jats:styled-content style=\"fixed-case\">cTNT<\/jats:styled-content> encoded by gene <jats:italic><jats:styled-content style=\"fixed-case\">TNNT<\/jats:styled-content>2<\/jats:italic>) has not. Using gene\u2010specific antisense oligonucleotides, we have investigated the role of <jats:styled-content style=\"fixed-case\">cTNT<\/jats:styled-content> in chick cardiogenesis. <jats:italic><jats:styled-content style=\"fixed-case\">TNNT<\/jats:styled-content>2<\/jats:italic> is expressed throughout heart development and in the postnatal heart. <jats:styled-content style=\"fixed-case\">TNNT<\/jats:styled-content>2\u2010morpholino treatment resulted in abnormal atrial septal growth and a reduction in the number of trabeculae in the developing primitive ventricular chamber. External analysis revealed the development of diverticula from the ventricular myocardial wall which showed no evidence of fibrosis and still retained a myocardial phenotype. Sarcomeric assembly appeared normal in these treated hearts. In humans, congenital ventricular diverticulum is a rare condition, which has not yet been genetically associated. However, abnormal haemodynamics is known to cause structural defects in the heart. Further, structural defects, including atrial septal defects and congenital diverticula, have previously been associated with conduction anomalies. Therefore, to provide mechanistic insights into the effect that cTNT knockdown has on the developing heart, quantitative <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> was performed to determine the expression of the shear stress responsive gene <jats:italic><jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>3<\/jats:italic> and the conduction gene <jats:italic><jats:styled-content style=\"fixed-case\">TBX<\/jats:styled-content>3<\/jats:italic>. Both genes were differentially expressed compared to controls. Therefore, a reduction in <jats:styled-content style=\"fixed-case\">cTNT<\/jats:styled-content> in the developing heart results in abnormal atrial septal formation and aberrant ventricular morphogenesis. We hypothesize that alterations to the haemodynamics, indicated by differential <jats:italic><jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>3<\/jats:italic> expression, causes these abnormalities in growth in cTNT knockdown hearts. In addition, the muscular diverticula reported here suggest a novel role for mutations of structural sarcomeric proteins in the pathogenesis of congenital cardiac diverticula. From these studies, we suggest <jats:italic>TNNT2<\/jats:italic> is a gene worthy of screening for those with a congenital heart defect, particularly atrial septal defects and ventricular diverticula.<\/jats:p>","DOI":"10.1111\/joa.12486","type":"journal-article","created":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T18:23:24Z","timestamp":1463682204000},"page":"436-449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<i>Cardiac troponin T<\/i> is necessary for normal development in the embryonic chick heart"],"prefix":"10.1111","volume":"229","author":[{"given":"Jennifer","family":"England","sequence":"first","affiliation":[{"name":"School of Life Sciences Medical School University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kar Lai","family":"Pang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Medical School University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Parnall","sequence":"additional","affiliation":[{"name":"School of Life Sciences Medical School University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Isabel","family":"Haig","sequence":"additional","affiliation":[{"name":"School of Life Sciences Medical School University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan","family":"Loughna","sequence":"additional","affiliation":[{"name":"School of Life Sciences Medical School University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002642"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.69.5.1226"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.76.4.681"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.169565"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0000000000000134"},{"key":"e_1_2_6_7_1","volume-title":"The Atlas of Chick Development","author":"Bellairs R","year":"2005"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.117.6.1740"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.09.017"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232877"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001362"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.15406\/jpnc.2014.01.00016"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1526"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8175.2006.00312.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1131-1"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000024114.82981.EA"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115165109"},{"key":"e_1_2_6_18_1","first-page":"1101","article-title":"Studies of heart development in normal and cardiac lethal mutant axolotls: a review","volume":"3","author":"Fransen ME","year":"1989","journal-title":"Scanning Microsc"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.111.961086"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000171901.40952.0d"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1050880104"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001950404"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"9971","DOI":"10.1016\/S0021-9258(18)61061-0","article-title":"The effects of troponin T fragments T1 and T2 on the binding of nonpolymerizable tropomyosin to F\u2010actin in the presence and absence of troponin I and troponin C","volume":"262","author":"Heeley DH","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00218-1"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.781"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.01.030"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.416007"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01282"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.04.039"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.11.018"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00092.2006"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-21"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2012.04.004"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.21.1.101"},{"key":"e_1_2_6_35_1","first-page":"91","article-title":"Inherited cardiomyopathies caused by troponin mutations","volume":"10","author":"Lu QW","year":"2013","journal-title":"J Geriatr Cardiol"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2005.09.046"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(96)00180-4"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm302"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.76.4.687"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000258019.74591.b3"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914888107"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1159\/000092634"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.03.050"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0066-782X2005000200016"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2009.01079.x"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.059063"},{"key":"e_1_2_6_47_1","first-page":"229","article-title":"Congenital left ventricular diverticulum associated with ASD, VSD, and epigastric hernia","volume":"3","author":"Shahmohammadi A","year":"2008","journal-title":"J Tehran Heart Cent"},{"key":"e_1_2_6_48_1","first-page":"38","article-title":"Control of myofilament activation in heart failure","volume":"87","author":"Solaro RJ","year":"1993","journal-title":"Circulation"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1053\/euje.2001.0090"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccd.1810260108"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199504203321603"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124883"}],"container-title":["Journal of Anatomy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjoa.12486","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjoa.12486","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joa.12486","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T03:17:19Z","timestamp":1696216639000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joa.12486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,19]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1111\/joa.12486"],"URL":"https:\/\/doi.org\/10.1111\/joa.12486","archive":["Portico"],"relation":{},"ISSN":["0021-8782","1469-7580"],"issn-type":[{"value":"0021-8782","type":"print"},{"value":"1469-7580","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,19]]},"assertion":[{"value":"2016-03-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}