{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:01:42Z","timestamp":1791219702130,"version":"4.1.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T00:00:00Z","timestamp":1470960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0161067","type":"journal-article","created":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T17:29:58Z","timestamp":1471022998000},"page":"e0161067","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development"],"prefix":"10.1371","volume":"11","author":[{"given":"Yumiko","family":"Togo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsu","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honoka","family":"Kiso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Tsukamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoko","family":"Yanagita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Sugai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemitsu","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Komori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"MacDougall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Bessho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,8,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1101\/gad.9.6.700","article-title":"Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate","volume":"9","author":"P Zhou","year":"1995","journal-title":"Genes Dev"},{"key":"ref2","first-page":"607","article-title":"Craniofacial abnormalities in homozygous Small eye (Sey\/Sey) embryos and newborn mice","volume":"186","author":"MH Kaufman","year":"1995","journal-title":"J Anat"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0012-1606(03)00157-X","article-title":"Stimulation of ectodermal organ development by Ectodysplasin-A1","volume":"259","author":"T Mustonen","year":"2003","journal-title":"Dev Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/dvdy.10289","article-title":"Loss of the Tg737 protein results in skeletal patterning defects","volume":"227","author":"Q Zhang","year":"2003","journal-title":"Dev Dyn"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/dvdy.20138","article-title":"Tooth patterning and enamel formation can be manipulated by misexpression of TNF receptor Edar","volume":"231","author":"J Pispa","year":"2004","journal-title":"Dev dyn"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ydbio.2003.12.019","article-title":"The activation level of the TNF family receptor, Edar, determines cusp number and tooth number during tooth development","volume":"268","author":"AS Tucker","year":"2004","journal-title":"Dev Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.devcel.2006.05.014","article-title":"Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling","volume":"11","author":"OD Klein","year":"2006","journal-title":"Dev Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"18627","DOI":"10.1073\/pnas.0607289103","article-title":"Continuous tooth generation in mouse is induced by activated epithelial Wnt\/beta-catenin signaling","volume":"103","author":"E J\u00e4rvinen","year":"2006","journal-title":"Proc Nati Acad Sci (USA)"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.bbrc.2007.05.148","article-title":"Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1 abrogation","volume":"359","author":"A Murashima-Suginami","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"4825","DOI":"10.1074\/jbc.M708388200","article-title":"Transcription factor epiprofin is essential for tooth morphogenesis by regulating epithelial cell fate and tooth number","volume":"283","author":"T Nakamura","year":"2008","journal-title":"J Biol Chem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"e4092","DOI":"10.1371\/journal.pone.0004092","article-title":"Lrp4 modulates extracellular integration of cell signaling pathways in development","volume":"3","author":"A Ohazama","year":"2008","journal-title":"PLoS One"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1126\/science.1167418","article-title":"Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row","volume":"323","author":"Z Zhang","year":"2009","journal-title":"Science"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1601-0825.2012.01963.x","article-title":"Phenotypes of CCAAT\/enhancer-binding protein beta deficiency: hyperdontia and elongated coronoid process","volume":"19","author":"B Huang","year":"2013","journal-title":"Oral Dis"},{"key":"ref14","first-page":"727","article-title":"Gene therapy: tools and potential applications","author":"K Takahashi","year":"2013"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.bbrc.2008.02.135","article-title":"Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse","volume":"369","author":"A Murashima-Suginami","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1242\/dev.033803","article-title":"Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood","volume":"136","author":"XP Wang","year":"2009","journal-title":"Development"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.archoralbio.2004.11.010","article-title":"Characteristic tissue interaction of the diastema region in mice","volume":"50","author":"H Yamamoto","year":"2005","journal-title":"Arch Oral Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/jez.b.22502","article-title":"The dynamics of supernumerary tooth development are differentially regulated by Sprouty genes","volume":"320","author":"S Lagronova-Churava","year":"2013","journal-title":"J Exp Zool B Mol Dev evol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.bbrc.2004.02.075","article-title":"USAG-1: a bone morphogenetic protein antagonist abundantly expressed in the kidney","volume":"316","author":"M Yanagita","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1172\/JCI25445","article-title":"Uterine sensitization-associated gene-1 (USAG-1), a novel BMP antagonist expressed in the kidney, accelerates tubular injury","volume":"116","author":"M Yanagita","year":"2006","journal-title":"J Clin Invsest"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/sj.ki.5001731","article-title":"Modulator of bone morphogenetic protein activity in the progression of kidney diseases","volume":"70","author":"M Yanagita","year":"2006","journal-title":"Kidney Int"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e96938","DOI":"10.1371\/journal.pone.0096938","article-title":"Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1) regulate supernumerary organ formations","volume":"9","author":"H Kiso","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"ref23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0722.2007.00504.x","article-title":"Mouse models of tooth abnormalities","volume":"116","author":"J Fleischmannova","year":"2008","journal-title":"Eur J Oral Sci"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1101\/gad.12.17.2735","article-title":"Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities","volume":"12","author":"H Peters","year":"1998","journal-title":"Genes Dev"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/ng0494-348","article-title":"Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development","volume":"6","author":"I Satokata","year":"1994","journal-title":"Nat Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1101\/gad.8.22.2691","article-title":"Development of several organs that require inductive epithelia-mesenchymal interactions in impaired in LEF-1-deficient mice","volume":"8","author":"C van Genderen","year":"1994","journal-title":"Genes Dev"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1242\/dev.126.13.2911","article-title":"Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice","volume":"126","author":"RN D'Souza","year":"1999","journal-title":"Development"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S0092-8674(00)80260-3","article-title":"Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia","volume":"30","author":"S Mundlos","year":"1997","journal-title":"Cell"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1177\/154405910508400206","article-title":"Runx2(Cbfa1) inhibits Shh signaling in the lower but not upper molars of mouse embryos and prevents the budding of putative successional teeth","volume":"84","author":"XP Wang","year":"2005","journal-title":"J Dent Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/002215540405200113","article-title":"Phenotypic changes in dentition of Runx2 Homozygote-null mutant mice","volume":"52","author":"T Aberg","year":"2004","journal-title":"J Histochem Cytochem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1126\/science.1116848","article-title":"Regulation of mammalian tooth cusp patterning by ectodin","volume":"23","author":"Y Kassai","year":"2005","journal-title":"Science"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1080\/03008200290000691","article-title":"Spatial expression of Cbfa1\/Runx2 isoforms in teeth and characterization of binding sites in the DSPP gene","volume":"43","author":"S Chen","year":"2002","journal-title":"Connect Tissue Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.bone.2005.10.026","article-title":"Type II\/III Runx2\/Cbfa1 is required for tooth germ development","volume":"38","author":"I Kobayashi","year":"2006","journal-title":"Bone"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0925-4773(98)00232-9","article-title":"Expression of core binding factor Osf2\/Cbfa-1 and bone sialoprotein in tooth development","volume":"81","author":"H Jiang","year":"1999","journal-title":"Mech Dev"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.gep.2012.07.001","article-title":"Expression pattern of Sox2 during mouse tooth development","volume":"12","author":"L Zhang","year":"2012","journal-title":"Gene Expr Patterns"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.devcel.2012.05.012","article-title":"Sox2+ stem cells contribute to all epithelial lineages of the tooth via Sfrp5+ progenitors","volume":"23","author":"E Juuri","year":"2012","journal-title":"Dev Cell"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1242\/dev.089599","article-title":"Sox2 marks epithelial competence to generate teeth in mammals and reptiles","volume":"140","author":"E Juuri","year":"2013","journal-title":"Development"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1371\/journal.pbio.0050159","article-title":"An integrated gene regulatory network controls stem cell proliferation in teeth","volume":"25","author":"XP Wang","year":"2007","journal-title":"PLoS Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0092-8674(00)80258-5","article-title":"Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts","volume":"89","author":"T Komori","year":"1997","journal-title":"Cell"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0092-8674(00)80257-3","article-title":"Osf2\/Cbfa1: a transcriptional activator of osteoblast differentiation","volume":"89","author":"P Ducy","year":"1997","journal-title":"Cell"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0003-9969(73)90162-3","article-title":"Deciduous incisor teeth of the mouse (Mus musculus)","volume":"18","author":"LR Fitzgerald","year":"1973","journal-title":"Arch Oral Biol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ydbio.2003.08.011","article-title":"Identification of a secreted BMP antagonist ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot","volume":"64","author":"J Laurikkala","year":"2003","journal-title":"Dev Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1242\/dev.00674","article-title":"Wise, a context-dependent activator and inhibitor of Wnt signalling","volume":"130","author":"N Itasaki","year":"2003","journal-title":"Development"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1600-0722.2006.00399.x","article-title":"Runx2 and dental development","volume":"114","author":"S Camilleri","year":"2006","journal-title":"Eur J Oral Sci"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1177\/0022034509342873","article-title":"Runx2, osx, and dspp in tooth development","volume":"88","author":"S Chen","year":"2009","journal-title":"J Dent Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1002\/stem.722","article-title":"Core binding factor beta functions in the maintenance of stem cells and orchestrates continuous proliferation and differentiation in mouse incisors","volume":"29","author":"H Kurosaka","year":"2011","journal-title":"Stem Cells"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1002\/jcp.22597","article-title":"Functional role of Rho-kinase in ameloblast differentiation","volume":"226","author":"K Otsu","year":"2011","journal-title":"J Cell Physiol"},{"key":"ref48","article-title":"A new phenotypic variant in cleidocranial dysplasia (CCD) associated with mutation c.391C>T of the RUNX2 gene","volume":"5","author":"M Callea","year":"2012","journal-title":"BMJ Case Rep"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/nm861","article-title":"Permanent correction of an inherited ectodermal dysplasia with recombinant EDA","volume":"9","author":"O Gaide","year":"2003","journal-title":"Nat Med"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1086\/521988","article-title":"Significant correction of disease after postnatal administration of recombinant ectodysplasin A in canine X-linked ectodermal dysplasia","volume":"81","author":"ML Casal","year":"2007","journal-title":"Am J Hum Genet"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1002\/ajmg.a.32916","article-title":"Neonatal treatment with recombinant ectodysplasin prevents respiratory disease in dogs with X-linked ectodermal dysplasia","volume":"149A","author":"EA Mauldin","year":"2009","journal-title":"Am J Med Genet A"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"30769","DOI":"10.1074\/jbc.M111.267997","article-title":"Molecular and therapeutic characterization of anti-ectodysplasin A receptor (EDAR) agonist monoclonal antibodies","volume":"286","author":"C Kowalczyk","year":"2001","journal-title":"J Biol Chem"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0161067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T22:13:22Z","timestamp":1657059202000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0161067"}},"subtitle":[],"editor":[{"given":"Paul Eckhard","family":"Witten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,8,12]]},"references-count":52,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0161067","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,12]]}}}