{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:41:11Z","timestamp":1791229271888,"version":"4.1.0"},"reference-count":49,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":2329,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:p>Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail-chick chimeras involving fate-mapping of neural crest cells to the ultimobranchial glands that regulate Ca2+ homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development implicates a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. In similarity with many gut endoderm derivatives embryonic C cells were found to co-express pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis differential Foxa1\/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo consistent with a growth-promoting role of Foxa1. Contrasting embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment down-regulated Foxa2 foregoing epithelial-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm, and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development.<\/jats:p>","DOI":"10.1242\/dev.126581","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T23:38:24Z","timestamp":1442965104000},"source":"Crossref","is-referenced-by-count":80,"title":["Revising the embryonic origin of thyroid C cells"],"prefix":"10.1242","author":[{"given":"Ellen","family":"Johansson","sequence":"first","affiliation":[{"name":"Sahlgrenska Cancer Center, Institute of Biomedicine, University of Gothenburg, SE-40530 G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Andersson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Cancer Center, Institute of Biomedicine, University of Gothenburg, SE-40530 G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"\u00d6rnros","sequence":"additional","affiliation":[{"name":"Sahlgrenska Cancer Center, Institute of Biomedicine, University of Gothenburg, SE-40530 G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Cancer Center, Institute of Biomedicine, University of Gothenburg, SE-40530 G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Ingeson-Carlsson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Cancer Center, Institute of Biomedicine, University of Gothenburg, SE-40530 G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Liang","sequence":"additional","affiliation":[{"name":"Sahlgrenska Cancer Center, Institute of Biomedicine, University of Gothenburg, SE-40530 G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Dahlberg","sequence":"additional","affiliation":[{"name":"Department of Surgery, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svante","family":"Jansson","sequence":"additional","affiliation":[{"name":"Department of Surgery, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Parrillo","sequence":"additional","affiliation":[{"name":"IRGS, Biogem, Ariano Irpino (AV), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Zoppoli","sequence":"additional","affiliation":[{"name":"Institute for Cancer Genetics, Columbia University, 1130 St. Nicholas Ave, 10031, New York (NY), USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo O.","family":"Barila","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, 15261 Pittsburgh (PA), USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Altschuler","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, 15261 Pittsburgh (PA), USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Padula","sequence":"additional","affiliation":[{"name":"Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, German Research Center for Environmental Health GmgH, Ingolstaedter Landstr. 1, 85764 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Lickert","sequence":"additional","affiliation":[{"name":"Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, German Research Center for Environmental Health GmgH, Ingolstaedter Landstr. 1, 85764 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Fagman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Cancer Center, Institute of Biomedicine, University of Gothenburg, SE-40530 G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042608113508200_DEV126581C1","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1007\/s12022-009-9070-6","article-title":"Review: the role of neural crest cells in the endocrine system","volume":"20","author":"Adams","year":"2009","journal-title":"Endocr. Pathol."},{"key":"2021042608113508200_DEV126581C2","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/nrm3625","article-title":"Unravelling stem cell dynamics by lineage tracing","volume":"14","author":"Blanpain","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042608113508200_DEV126581C3","doi-asserted-by":"publisher","first-page":"e1002770","DOI":"10.1371\/journal.pgen.1002770","article-title":"Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2","volume":"8","author":"Bochkis","year":"2012","journal-title":"PLoS Genet."},{"key":"2021042608113508200_DEV126581C4","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.devcel.2011.07.019","article-title":"Tracing cells for tracking cell lineage and clonal behavior","volume":"21","author":"Buckingham","year":"2011","journal-title":"Dev. Cell"},{"key":"2021042608113508200_DEV126581C5","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1242\/dev.028415","article-title":"Foxa2 regulates polarity and epithelialization in the endoderm germ layer of the mouse embryo","volume":"136","author":"Burtscher","year":"2009","journal-title":"Development"},{"key":"2021042608113508200_DEV126581C6","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1242\/dev.127.8.1671","article-title":"Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis","volume":"127","author":"Chai","year":"2000","journal-title":"Development"},{"key":"2021042608113508200_DEV126581C7","doi-asserted-by":"publisher","first-page":"236","DOI":"10.2353\/ajpath.2008.070602","article-title":"Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer","volume":"172","author":"Chiaverotti","year":"2008","journal-title":"Am. J. Pathol."},{"key":"2021042608113508200_DEV126581C8","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1126\/science.158.3803.924","article-title":"Calcitonin from ultimobranchial glands of dogfish and chickens","volume":"158","author":"Copp","year":"1967","journal-title":"Science"},{"key":"2021042608113508200_DEV126581C9","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1002\/bies.20767","article-title":"The origin and evolution of the neural crest","volume":"30","author":"Donoghue","year":"2008","journal-title":"Bioessays"},{"key":"2021042608113508200_DEV126581C10","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/978-0-387-46954-6_6","article-title":"The contribution of the neural crest to the vertebrate body","volume":"589","author":"Dupin","year":"2006","journal-title":"Adv. Exp. Med. Biol."},{"key":"2021042608113508200_DEV126581C11","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1002\/dvg.20540","article-title":"Sox17-2A-iCre: a knock-in mouse line expressing Cre recombinase in endoderm and vascular endothelial cells","volume":"47","author":"Engert","year":"2009","journal-title":"Genesis"},{"key":"2021042608113508200_DEV126581C12","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1002\/dvdy.20653","article-title":"The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation","volume":"235","author":"Fagman","year":"2006","journal-title":"Dev. Dyn."},{"key":"2021042608113508200_DEV126581C13","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.ydbio.2011.08.015","article-title":"Gene expression profiling at early organogenesis reveals both common and diverse mechanisms in foregut patterning","volume":"359","author":"Fagman","year":"2011","journal-title":"Dev. Biol."},{"key":"2021042608113508200_DEV126581C14","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1111\/j.1469-7580.2010.01232.x","article-title":"Developmental homoplasy: convergence in cellular differentiation","volume":"216","author":"Graham","year":"2010","journal-title":"J. Anat."},{"key":"2021042608113508200_DEV126581C15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/2041-9139-3-24","article-title":"Developmental and evolutionary origins of the pharyngeal apparatus","volume":"3","author":"Graham","year":"2012","journal-title":"Evodevo"},{"key":"2021042608113508200_DEV126581C16","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.1365-2559.1983.tb02218.x","article-title":"Glandular (tubular and follicular) variants of medullary carcinoma of the thyroid","volume":"7","author":"Harach","year":"1983","journal-title":"Histopathology"},{"key":"2021042608113508200_DEV126581C17","doi-asserted-by":"publisher","first-page":"7356","DOI":"10.1073\/pnas.1203605109","article-title":"Mind bomb 1 is required for pancreatic beta-cell formation","volume":"109","author":"Horn","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042608113508200_DEV126581C18","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/40146","article-title":"Wnt signalling required for expansion of neural crest and CNS progenitors","volume":"389","author":"Ikeya","year":"1997","journal-title":"Nature"},{"key":"2021042608113508200_DEV126581C19","doi-asserted-by":"publisher","first-page":"9901","DOI":"10.1073\/pnas.0500756102","article-title":"An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers","volume":"102","author":"Ippolito","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042608113508200_DEV126581C50","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","article-title":"Exploration, normalization, and summaries of high density oligonucleotide array probe level data","volume":"4","author":"Irizarry","year":"2003","journal-title":"Biostatistics"},{"key":"2021042608113508200_DEV126581C20","doi-asserted-by":"publisher","first-page":"3907","DOI":"10.1158\/0008-5472.CAN-03-3801","article-title":"Expression profiles provide insights into early malignant potential and skeletal abnormalities in multiple endocrine neoplasia type 2B syndrome tumors","volume":"64","author":"Jain","year":"2004","journal-title":"Cancer Res."},{"key":"2021042608113508200_DEV126581C21","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1242\/dev.127.8.1607","article-title":"Fate of the mammalian cardiac neural crest","volume":"127","author":"Jiang","year":"2000","journal-title":"Development"},{"key":"2021042608113508200_DEV126581C22","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1002\/stem.525","article-title":"Convergent genesis of an adult neural crest-like dermal stem cell from distinct developmental origins","volume":"28","author":"Jinno","year":"2010","journal-title":"Stem Cells"},{"key":"2021042608113508200_DEV126581C23","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.gde.2010.06.005","article-title":"The FoxA factors in organogenesis and differentiation","volume":"20","author":"Kaestner","year":"2010","journal-title":"Curr. Opin. Genet. Dev."},{"key":"2021042608113508200_DEV126581C24","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1369\/jhc.7A7179.2007","article-title":"Expression of the epithelial marker E-cadherin by thyroid C cells and their precursors during murine development","volume":"55","author":"Kameda","year":"2007","journal-title":"J. Histochem. Cytochem."},{"key":"2021042608113508200_DEV126581C25","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.humpath.2004.01.017","article-title":"Forkhead box A2 transcription factor is expressed in all types of neuroendocrine lung tumors","volume":"35","author":"Khoor","year":"2004","journal-title":"Hum. Pathol."},{"key":"2021042608113508200_DEV126581C26","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1002\/dvdy.20655","article-title":"Origin of the ultimobranchial body cyst: T\/ebp\/Nkx2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid","volume":"235","author":"Kusakabe","year":"2006","journal-title":"Dev. Dyn."},{"key":"2021042608113508200_DEV126581C27","first-page":"2857","article-title":"[Demonstration of neural origin of calcitonin cells of ultimobranchial body of chick embryo]","volume":"270","author":"Le Douarin","year":"1970","journal-title":"C. R. Acad. Sci. Hebd. Seances Acad. Sci. D"},{"key":"2021042608113508200_DEV126581C28","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1038\/nature03649","article-title":"The initiation of liver development is dependent on Foxa transcription factors","volume":"435","author":"Lee","year":"2005","journal-title":"Nature"},{"key":"2021042608113508200_DEV126581C29","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1093\/hmg\/ddh176","article-title":"Full spectrum of malformations in velo-cardio-facial syndrome\/DiGeorge syndrome mouse models by altering Tbx1 dosage","volume":"13","author":"Liao","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2021042608113508200_DEV126581C30","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.modgep.2007.03.002","article-title":"A high-resolution anatomical ontology of the developing murine genitourinary tract","volume":"7","author":"Little","year":"2007","journal-title":"Gene Expr. Patterns"},{"key":"2021042608113508200_DEV126581C31","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/ng0598-87","article-title":"Follicular cells of the thyroid gland require Pax8 gene function","volume":"19","author":"Mansouri","year":"1998","journal-title":"Nat. Genet."},{"key":"2021042608113508200_DEV126581C32","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1016\/S0002-9440(10)65453-3","article-title":"Mixed medullary and follicular carcinoma of the thyroid: on the search for its histogenesis","volume":"155","author":"Matias-Guiu","year":"1999","journal-title":"Am. J. Pathol."},{"key":"2021042608113508200_DEV126581C33","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/dvg.20335","article-title":"A global double-fluorescent Cre reporter mouse","volume":"45","author":"Muzumdar","year":"2007","journal-title":"Genesis"},{"key":"2021042608113508200_DEV126581C34","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.clon.2010.05.002","article-title":"Medullary thyroid carcinoma","volume":"22","author":"Pacini","year":"2010","journal-title":"Clin. Oncol."},{"key":"2021042608113508200_DEV126581C35","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/214929a0","article-title":"Cytochemical evidence for an ultimobranchial origin of rodent thyroid C cells","volume":"214","author":"Pearse","year":"1967","journal-title":"Nature"},{"key":"2021042608113508200_DEV126581C36","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/BF00501955","article-title":"Immunocytochemical confirmation of the neural crest origin of avian calcitonin-producing cells","volume":"40","author":"Polak","year":"1974","journal-title":"Histochemistry"},{"key":"2021042608113508200_DEV126581C37","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3109\/15513819309048236","article-title":"Thyroid C cells in the DiGeorge anomaly: a quantitative study","volume":"13","author":"Pueblitz","year":"1993","journal-title":"Fetal Pediatr. Pathol."},{"key":"2021042608113508200_DEV126581C38","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ccr.2010.05.024","article-title":"Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine phenotype and neuroendocrine prostate tumors","volume":"18","author":"Qi","year":"2010","journal-title":"Cancer Cell"},{"key":"2021042608113508200_DEV126581C39","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1158\/0008-5472.CAN-09-2979","article-title":"Loss of FOXA1\/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer","volume":"70","author":"Song","year":"2010","journal-title":"Cancer Res."},{"key":"2021042608113508200_DEV126581C40","doi-asserted-by":"publisher","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":"2021042608113508200_DEV126581C41","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/cr.2010.126","article-title":"FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers","volume":"21","author":"Tang","year":"2011","journal-title":"Cell Res."},{"key":"2021042608113508200_DEV126581C42","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1073\/pnas.58.4.1684","article-title":"The ultimobranchial origin of thyrocalcitonin","volume":"58","author":"Tauber","year":"1967","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042608113508200_DEV126581C43","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.ccr.2013.03.004","article-title":"Tumor dissemination: an EMT affair","volume":"23","author":"Thiery","year":"2013","journal-title":"Cancer Cell"},{"key":"2021042608113508200_DEV126581C44","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1210\/jc.2011-2772","article-title":"Evidence for calcitonin-producing cells in human lingual thyroids","volume":"97","author":"Vandernoot","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2021042608113508200_DEV126581C45","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1017\/S1464793106007068","article-title":"Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest","volume":"81","author":"Vickaryous","year":"2006","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"2021042608113508200_DEV126581C46","doi-asserted-by":"publisher","first-page":"49948","DOI":"10.1074\/jbc.M406659200","article-title":"Regulation of the cell-specific calcitonin\/calcitonin gene-related peptide enhancer by USF and the Foxa2 forkhead protein","volume":"279","author":"Viney","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2021042608113508200_DEV126581C47","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1093\/hmg\/11.8.915","article-title":"Tbx1 mutation causes multiple cardiovascular defects and disrupts neural crest and cranial nerve migratory pathways","volume":"11","author":"Vitelli","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"2021042608113508200_DEV126581C48","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1126\/science.1228522","article-title":"Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition","volume":"339","author":"Yu","year":"2013","journal-title":"Science"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/142\/20\/3519\/1838927\/dev126581.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.126581\/2033745\/dev_126581v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.126581\/2033745\/dev_126581v1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T16:50:25Z","timestamp":1621356625000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/doi\/10.1242\/dev.126581\/256824\/Revising-the-embryonic-origin-of-thyroid-C-cells"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,1]]},"references-count":49,"URL":"https:\/\/doi.org\/10.1242\/dev.126581","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725803620.793540661","asserted-by":"object"}]},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2015,1,1]]},"article-number":"dev.126581"}}