{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:43:37Z","timestamp":1792691017826,"version":"4.5.0"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5K12DE023583-05"],"award-info":[{"award-number":["5K12DE023583-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006474","name":"Columbia University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006474","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011544","name":"College of Dental Medicine, Columbia University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011544","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Developmental Biology"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1016\/j.ydbio.2021.05.011","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T12:27:28Z","timestamp":1622118448000},"page":"241-250","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["mTOR deletion in neural crest cells disrupts cardiac outflow tract remodeling and causes a spectrum of cardiac defects through the mTORC1 pathway"],"prefix":"10.1016","volume":"477","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3594-4020","authenticated-orcid":false,"given":"Xuguang","family":"Nie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Ricupero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy J.","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ydbio.2021.05.011_bib1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/cr.2012.11","article-title":"Neural crest stem cells: discovery, properties and potential for therapy","volume":"22","author":"Achilleos","year":"2012","journal-title":"Cell Res."},{"key":"10.1016\/j.ydbio.2021.05.011_bib2","doi-asserted-by":"crossref","first-page":"pe27","DOI":"10.1126\/scisignal.267pe27","article-title":"New insights into mTOR signaling: mTORC2 and beyond","volume":"2","author":"Alessi","year":"2009","journal-title":"Sci. Signal."},{"key":"10.1016\/j.ydbio.2021.05.011_bib3","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbrc.2011.08.034","article-title":"Endoplasmic reticulum is a main localization site of mTORC2","volume":"413","author":"Boulbes","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ydbio.2021.05.011_bib4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/bs.ctdb.2015.12.003","article-title":"The neural crest migrating into the Twenty-first century","volume":"116","author":"Bronner","year":"2016","journal-title":"Curr. Top. Dev. Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib5","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1242\/dev.01197","article-title":"Cardiac neural crest of the mouse embryo: axial level of origin, migratory pathway and cell autonomy of the splotch (Sp2H) mutant effect","volume":"131","author":"Chan","year":"2004","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2021.05.011_bib6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/jbmr.2348","article-title":"mTORC2 signaling promotes skeletal growth and bone formation in mice","volume":"30","author":"Chen","year":"2015","journal-title":"J.\u00a0Bone Miner. Res."},{"key":"10.1016\/j.ydbio.2021.05.011_bib7","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1242\/dev.108811","article-title":"mTORC1 signaling controls mammalian skeletal growth through stimulation of protein synthesis","volume":"141","author":"Chen","year":"2014","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2021.05.011_bib8","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1074\/jbc.M807745200","article-title":"Cdc42-mTOR signaling pathway controls Hes5 and Pax6 expression in retinoic acid-dependent neural differentiation","volume":"284","author":"Endo","year":"2009","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ydbio.2021.05.011_bib9","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/jbmr.2447","article-title":"Neural crest-specific TSC1 deletion in mice leads to sclerotic craniofacial bone lesion","volume":"30","author":"Fang","year":"2015","journal-title":"J.\u00a0Bone Miner. Res."},{"key":"10.1016\/j.ydbio.2021.05.011_bib10","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1016\/j.cub.2003.11.021","article-title":"PLD1 regulates mTOR signaling and mediates Cdc42 activation of S6K1","volume":"13","author":"Fang","year":"2003","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib11","doi-asserted-by":"crossref","first-page":"9508","DOI":"10.1128\/MCB.24.21.9508-9516.2004","article-title":"Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development","volume":"24","author":"Gangloff","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib12","doi-asserted-by":"crossref","first-page":"43928","DOI":"10.1074\/jbc.R112.406942","article-title":"Mammalian target of rapamycin (mTOR) signaling network in skeletal myogenesis","volume":"287","author":"Ge","year":"2012","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ydbio.2021.05.011_bib13","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.devcel.2006.10.007","article-title":"Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1","volume":"11","author":"Guertin","year":"2006","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2021.05.011_bib14","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1101\/gad.1212704","article-title":"Upstream and downstream of mTOR","volume":"18","author":"Hay","year":"2004","journal-title":"Genes Dev."},{"key":"10.1016\/j.ydbio.2021.05.011_bib15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.semcdb.2006.12.004","article-title":"Model systems for the study of heart development and disease. Cardiac neural crest and conotruncal malformations","volume":"18","author":"Hutson","year":"2007","journal-title":"Semin. Cell Dev. Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib16","doi-asserted-by":"crossref","first-page":"4076","DOI":"10.1242\/dev.108282","article-title":"mTOR regulates brain morphogenesis by mediating GSK3 signaling","volume":"141","author":"Ka","year":"2014","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2021.05.011_bib17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.diff.2012.04.005","article-title":"The neural crest in cardiac congenital anomalies","volume":"84","author":"Keyte","year":"2012","journal-title":"Differentiation"},{"key":"10.1016\/j.ydbio.2021.05.011_bib18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1161\/01.RES.0000027135.63141.89","article-title":"Cardiac septation: a late contribution of the embryonic primary myocardium to heart morphogenesis","volume":"91","author":"Lamers","year":"2002","journal-title":"Circ. Res."},{"key":"10.1016\/j.ydbio.2021.05.011_bib19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.semcdb.2014.09.023","article-title":"mTOR signalling, embryogenesis and the control of lung development","volume":"36","author":"Land","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib20","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1242\/jcs.051011","article-title":"mTOR signaling at a glance","volume":"122","author":"Laplante","year":"2009","journal-title":"J.\u00a0Cell Sci."},{"key":"10.1016\/j.ydbio.2021.05.011_bib21","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.ydbio.2021.05.011_bib22","first-page":"1713","article-title":"Regulation of mTORC1 and its impact on gene expression at a glance","volume":"126","author":"Laplante","year":"2013","journal-title":"J.\u00a0Cell Sci."},{"key":"10.1016\/j.ydbio.2021.05.011_bib23","doi-asserted-by":"crossref","DOI":"10.1002\/mnfr.201700128","article-title":"Muscle metabolic alterations induced by genetic ablation of 4E-BP1 and 4E-BP2 in response to diet-induced obesity","volume":"61","author":"Le Bacquer","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"10.1016\/j.ydbio.2021.05.011_bib24","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ydbio.2013.04.026","article-title":"The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling","volume":"379","author":"Lewis","year":"2013","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib25","doi-asserted-by":"crossref","first-page":"38362","DOI":"10.1074\/jbc.M110.141168","article-title":"Rapamycin inhibits cytoskeleton reorganization and cell motility by suppressing RhoA expression and activity","volume":"285","author":"Liu","year":"2010","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ydbio.2021.05.011_bib26","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ydbio.2013.09.013","article-title":"Inactivation of Cdc42 in neural crest cells causes craniofacial and cardiovascular morphogenesis defects","volume":"383","author":"Liu","year":"2013","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.stem.2012.05.026","article-title":"Temporal changes in PTEN and mTORC2 regulation of hematopoietic stem cell self-renewal and leukemia suppression","volume":"11","author":"Magee","year":"2012","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ydbio.2021.05.011_bib28","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1093\/hmg\/ddq570","article-title":"Smooth muscle protein-22-mediated deletion of Tsc1 results in cardiac hypertrophy that is mTORC1-mediated and reversed by rapamycin","volume":"20","author":"Malhowski","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ydbio.2021.05.011_bib29","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1242\/dev.091751","article-title":"The neural crest","volume":"140","author":"Mayor","year":"2013","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2021.05.011_bib30","doi-asserted-by":"crossref","first-page":"473","DOI":"10.4161\/15384101.2014.991572","article-title":"mTOR coordinates protein synthesis, mitochondrial activity and proliferation","volume":"14","author":"Morita","year":"2015","journal-title":"Cell Cycle"},{"key":"10.1016\/j.ydbio.2021.05.011_bib31","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.ydbio.2008.02.006","article-title":"Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects","volume":"316","author":"Nie","year":"2008","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib32","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ydbio.2020.08.010","article-title":"mTOR plays a pivotal role in multiple processes of enamel organ development principally through the mTORC1 pathway and in part via regulating cytoskeleton dynamics","volume":"467","author":"Nie","year":"2020","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007491","article-title":"mTOR acts as a pivotal signaling hub for neural crest cells during craniofacial development","volume":"14","author":"Nie","year":"2018","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ydbio.2021.05.011_bib34","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.4161\/cc.10.14.16586","article-title":"mTOR complex 2 signaling and functions","volume":"10","author":"Oh","year":"2011","journal-title":"Cell Cycle"},{"key":"10.1016\/j.ydbio.2021.05.011_bib35","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1128\/MCB.24.8.3112-3124.2004","article-title":"S6K1(-\/-)\/S6K2(-\/-) mice exhibit perinatal lethality and rapamycin-sensitive 5'-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway","volume":"24","author":"Pende","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib36","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00335-013-9469-8","article-title":"Nuclear double-fluorescent reporter for in vivo and ex vivo analyses of biological transitions in mouse nuclei","volume":"24","author":"Prigge","year":"2013","journal-title":"Mamm. Genome"},{"key":"10.1016\/j.ydbio.2021.05.011_bib37","doi-asserted-by":"crossref","first-page":"27385","DOI":"10.1074\/jbc.M110.120295","article-title":"mTORC1 links protein quality and quantity control by sensing chaperone availability","volume":"285","author":"Qian","year":"2010","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ydbio.2021.05.011_bib38","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1083\/jcb.200903131","article-title":"Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy","volume":"187","author":"Risson","year":"2009","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.ydbio.2021.05.011_bib39","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-16662-1","article-title":"AKT-mTOR signaling modulates the dynamics of IRE1 RNAse activity by regulating ER-mitochondria contacts","volume":"7","author":"Sanchez-Alvarez","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ydbio.2021.05.011_bib40","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1161\/CIRCRESAHA.117.311147","article-title":"New insights into the role of mTOR signaling in the cardiovascular system","volume":"122","author":"Sciarretta","year":"2018","journal-title":"Circ. Res."},{"key":"10.1016\/j.ydbio.2021.05.011_bib41","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1161\/CIRCRESAHA.114.302022","article-title":"Mammalian target of rapamycin signaling in cardiac physiology and disease","volume":"114","author":"Sciarretta","year":"2014","journal-title":"Circ. Res."},{"key":"10.1016\/j.ydbio.2021.05.011_bib42","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.celrep.2015.03.010","article-title":"mTORC2 regulates cardiac response to stress by inhibiting MST1","volume":"11","author":"Sciarretta","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.ydbio.2021.05.011_bib43","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/nature09584","article-title":"mTORC1 controls fasting-induced ketogenesis and its modulation by ageing","volume":"468","author":"Sengupta","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2021.05.011_bib44","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.devcel.2006.08.013","article-title":"Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability","volume":"11","author":"Shiota","year":"2006","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2021.05.011_bib45","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1242\/dev.105445","article-title":"Establishing neural crest identity: a gene regulatory recipe","volume":"142","author":"Simoes-Costa","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2021.05.011_bib46","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/5007","article-title":"Generalized lacZ expression with the ROSA26 Cre reporter strain","volume":"21","author":"Soriano","year":"1999","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ydbio.2021.05.011_bib47","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.47929","article-title":"Cardiac neural crest contributes to cardiomyocytes in amniotes and heart regeneration in zebrafish","volume":"8","author":"Tang","year":"2019","journal-title":"Elife"},{"key":"10.1016\/j.ydbio.2021.05.011_bib48","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: from stress pathway to homeostatic regulation","volume":"334","author":"Walter","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.ydbio.2021.05.011_bib49","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1177\/0022034518779546","article-title":"Epithelial Cdc42 deletion induced enamel organ defects and cystogenesis","volume":"97","author":"Zheng","year":"2018","journal-title":"J.\u00a0Dent. Res."},{"key":"10.1016\/j.ydbio.2021.05.011_bib50","article-title":"Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth","volume":"8","author":"Zhu","year":"2013","journal-title":"PloS One"}],"container-title":["Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S001216062100124X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S001216062100124X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T04:48:06Z","timestamp":1757911686000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S001216062100124X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":50,"alternative-id":["S001216062100124X"],"URL":"https:\/\/doi.org\/10.1016\/j.ydbio.2021.05.011","relation":{},"ISSN":["0012-1606"],"issn-type":[{"value":"0012-1606","type":"print"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"mTOR deletion in neural crest cells disrupts cardiac outflow tract remodeling and causes a spectrum of cardiac defects through the mTORC1 pathway","name":"articletitle","label":"Article Title"},{"value":"Developmental Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ydbio.2021.05.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc.","name":"copyright","label":"Copyright"}]}}