{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:40:12Z","timestamp":1791322812763,"version":"4.3.1"},"reference-count":92,"publisher":"The Company of Biologists","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,15]]},"abstract":"<jats:p>TGF\u03b2\/BMP signaling regulates the fate of multipotential cranial neural crest (CNC) cells during tooth and jawbone formation as these cells differentiate into odontoblasts and osteoblasts, respectively. The functional significance of SMAD4, the common mediator of TGF\u03b2\/BMP signaling, in regulating the fate of CNC cells remains unclear. In this study, we investigated the mechanism of SMAD4 in regulating the fate of CNC-derived dental mesenchymal cells through tissue-specific inactivation of Smad4. Ablation of Smad4 results in defects in odontoblast differentiation and dentin formation. Moreover, ectopic bone-like structures replaced normal dentin in the teeth of Osr2-IresCre;Smad4fl\/fl mice. Despite the lack of dentin, enamel formation appeared unaffected in Osr2-IresCre;Smad4fl\/fl mice, challenging the paradigm that the initiation of enamel development depends on normal dentin formation. At the molecular level, loss of Smad4 results in downregulation of the WNT pathway inhibitors Dkk1 and Sfrp1 and in the upregulation of canonical WNT signaling, including increased \u03b2-catenin activity. More importantly, inhibition of the upregulated canonical WNT pathway in Osr2-IresCre;Smad4fl\/fl dental mesenchyme in vitro partially rescued the CNC cell fate change. Taken together, our study demonstrates that SMAD4 plays a crucial role in regulating the interplay between TGF\u03b2\/BMP and WNT signaling to ensure the proper CNC cell fate decision during organogenesis.<\/jats:p>","DOI":"10.1242\/dev.061341","type":"journal-article","created":{"date-parts":[[2011,4,14]],"date-time":"2011-04-14T00:46:14Z","timestamp":1302741974000},"page":"1977-1989","source":"Crossref","is-referenced-by-count":102,"title":["SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis"],"prefix":"10.1242","volume":"138","author":[{"given":"Jingyuan","family":"Li","sequence":"first","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA"},{"name":"Salivary Gland Disease Center and the Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Mayo","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Pablo","family":"Bringas","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rulang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Genetics and Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songling","family":"Wang","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and the Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chai","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042606522907500_R1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0002-9440(10)64539-7","article-title":"Nestin expression in embryonic and adult human teeth under normal and pathological conditions","volume":"157","author":"About","year":"2000","journal-title":"Am. J. Pathol."},{"key":"2021042606522907500_R2","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1086\/520064","article-title":"Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia","volume":"81","author":"Adaimy","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2021042606522907500_R3","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1242\/dev.054668","article-title":"Inhibition of Wnt signaling by Wise (Sostdc1) and negative feedback from Shh controls tooth number and patterning","volume":"137","author":"Ahn","year":"2010","journal-title":"Development"},{"key":"2021042606522907500_R4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0006-291X(02)02951-0","article-title":"Activated beta-catenin induces osteoblast differentiation of C3H10T1\/2 cells and participates in BMP2 mediated signal transduction","volume":"301","author":"Bain","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021042606522907500_R5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1136\/jmg.39.2.91","article-title":"Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease","volume":"39","author":"Balemans","year":"2002","journal-title":"J. Med. Genet."},{"key":"2021042606522907500_R6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1101\/gad.1044903","article-title":"Ectodermal Wnt3\/\u03b2-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge","volume":"17","author":"Barrow","year":"2003","journal-title":"Genes Dev."},{"key":"2021042606522907500_R7","first-page":"491","article-title":"Effects of dentin proteins, transforming growth factor beta 1 (TGF beta 1) and bone morphogenetic protein 2 (BMP2) on the differentiation of odontoblast in vitro","volume":"36","author":"B\u00e8gue-Kirn","year":"1992","journal-title":"Int. J. Dev. Biol."},{"key":"2021042606522907500_R8","first-page":"405","article-title":"Comparative analysis of TGF beta s, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation","volume":"38","author":"B\u00e8gue-Kirn","year":"1994","journal-title":"Int. J. Dev. Biol."},{"key":"2021042606522907500_R9","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1073\/pnas.0408742102","article-title":"Regulation of osteoblastogenesis and bone mass by Wnt10b","volume":"102","author":"Bennett","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606522907500_R10","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1210\/me.2003-0498","article-title":"The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice","volume":"18","author":"Bodine","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"2021042606522907500_R11","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1056\/NEJMoa013444","article-title":"High bone density due to a mutation in LDL-receptor-related protein 5","volume":"346","author":"Boyden","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"2021042606522907500_R12","first-page":"381","article-title":"Immunolocalization of acidic and basic fibroblast growth factors during mouse odontogenesis","volume":"36","author":"Cam","year":"1992","journal-title":"Int. J. Dev. Biol."},{"key":"2021042606522907500_R13","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/jemt.10287","article-title":"Prospects for tooth regeneration in the 21st century: a perspective","volume":"60","author":"Chai","year":"2003","journal-title":"Microsc. Res. Tech."},{"key":"2021042606522907500_R14","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":"2021042606522907500_R15","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ydbio.2009.07.015","article-title":"Wnt\/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development","volume":"334","author":"Chen","year":"2009","journal-title":"Dev. Biol."},{"key":"2021042606522907500_R16","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1242\/dev.122.10.3035","article-title":"Msx1 controls inductive signaling in mammalian tooth morphogenesis","volume":"122","author":"Chen","year":"1996","journal-title":"Development"},{"key":"2021042606522907500_R17","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1074\/jbc.M602700200","article-title":"\u03b2-Catenin signaling pathway is crucial for bone morphogenetic protein 2 to induce new bone formation","volume":"282","author":"Chen","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2021042606522907500_R18","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/stem.2","article-title":"Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development","volume":"27","author":"Chung","year":"2009","journal-title":"Stem Cells"},{"key":"2021042606522907500_R19","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/S0960-9822(07)00562-3","article-title":"Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase","volume":"8","author":"Danielian","year":"1998","journal-title":"Curr. Biol."},{"key":"2021042606522907500_R20","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1242\/dev.126.20.4557","article-title":"Multiple roles for activated LEF\/TCF transcription complexes during hair follicle development and differentiation","volume":"126","author":"DasGupta","year":"1999","journal-title":"Development"},{"key":"2021042606522907500_R21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1006\/dbio.1998.8992","article-title":"Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian tooth","volume":"202","author":"Dassule","year":"1998","journal-title":"Dev. Biol."},{"key":"2021042606522907500_R22","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ydbio.2005.07.034","article-title":"Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland","volume":"286","author":"Dean","year":"2005","journal-title":"Dev. Biol."},{"key":"2021042606522907500_R23","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/jez.b.21090","article-title":"Early evolution of vertebrate skeletal tissues and cellular interactions, and the canalization of skeletal development","volume":"306B","author":"Donoghue","year":"2006","journal-title":"J. Exp. Zool. B Mol. Dev. Evol."},{"key":"2021042606522907500_R24","doi-asserted-by":"crossref","first-page":"5285","DOI":"10.1242\/dev.127.24.5285","article-title":"The WNT antagonist cSFRP2 modulates programmed cell death in the developing hindbrain","volume":"127","author":"Ellies","year":"2000","journal-title":"Development"},{"key":"2021042606522907500_R25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/dvdy.20285","article-title":"Dynamic expression of Wnt signaling-related Dickkopf1, -2, and -3 mRNAs in the developing mouse tooth","volume":"233","author":"Fjeld","year":"2005","journal-title":"Dev. Dyn."},{"key":"2021042606522907500_R26","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1089\/hum.2005.16.1287","article-title":"Novel compound enables high-level adenovirus transduction in the absence of an adenovirus-specific receptor","volume":"16","author":"Fouletier-Dilling","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"2021042606522907500_R27","doi-asserted-by":"crossref","first-page":"5941","DOI":"10.1128\/MCB.00706-09","article-title":"Disruption of Smad4 in odontoblasts causes multiple keratocystic odontogenic tumors and tooth malformation in mice","volume":"29","author":"Gao","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"2021042606522907500_R28","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S0092-8674(01)00571-2","article-title":"LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development","volume":"107","author":"Gong","year":"2001","journal-title":"Cell"},{"key":"2021042606522907500_R29","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/emboj\/21.5.966","article-title":"The Wnt antagonist Dickkopf-1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death","volume":"21","author":"Grotewold","year":"2002","journal-title":"EMBO J."},{"key":"2021042606522907500_R30","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1101\/gad.1230704","article-title":"Wnt\/\u03b2-catenin signaling is sufficient and necessary for synovial joint formation","volume":"18","author":"Guo","year":"2004","journal-title":"Genes Dev."},{"key":"2021042606522907500_R31","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.archoralbio.2004.05.005","article-title":"TGF-[beta] activated Smad signalling leads to a Smad3-mediated down-regulation of DSPP in an odontoblast cell line","volume":"49","author":"He","year":"2004","journal-title":"Arch. Oral Biol."},{"key":"2021042606522907500_R32","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/ng1430","article-title":"BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling","volume":"36","author":"He","year":"2004","journal-title":"Nat. Genet."},{"key":"2021042606522907500_R33","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1359\/jbmr.040907","article-title":"Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6","volume":"19","author":"Holmen","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"2021042606522907500_R34","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/nature08356","article-title":"Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling","volume":"461","author":"Huang","year":"2009","journal-title":"Nature"},{"key":"2021042606522907500_R35","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0092-8674(01)00336-1","article-title":"beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin","volume":"105","author":"Huelsken","year":"2001","journal-title":"Cell"},{"key":"2021042606522907500_R36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0925-4773(99)00322-6","article-title":"Reiterative signaling and patterning during mammalian tooth morphogenesis","volume":"92","author":"Jernvall","year":"2000","journal-title":"Mech. Dev."},{"key":"2021042606522907500_R37","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1242\/dev.025825","article-title":"BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway","volume":"135","author":"Kamiya","year":"2008","journal-title":"Development"},{"key":"2021042606522907500_R38","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1359\/jbmr.090806","article-title":"Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts","volume":"25","author":"Kamiya","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"2021042606522907500_R39","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1432-0436.1985.tb00311.x","article-title":"Acellular dental matrices promote functional differentiation of ameloblasts","volume":"29","author":"Karcher-Djuricic","year":"1985","journal-title":"Differentiation"},{"key":"2021042606522907500_R40","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1083\/jcb.200201089","article-title":"Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor","volume":"157","author":"Kato","year":"2002","journal-title":"J. Cell Biol."},{"key":"2021042606522907500_R41","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1242\/jcs.00623","article-title":"Secreted antagonists of the Wnt signalling pathway","volume":"116","author":"Kawano","year":"2003","journal-title":"J. Cell Sci."},{"key":"2021042606522907500_R42","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1083\/jcb.200411095","article-title":"Neural crest stem cell maintenance by combinatorial Wnt and BMP signaling","volume":"169","author":"Kl\u00e9ber","year":"2005","journal-title":"J. Cell Biol."},{"key":"2021042606522907500_R43","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.ydbio.2007.09.050","article-title":"Smad4 is required to regulate the fate of cranial neural crest cells","volume":"312","author":"Ko","year":"2007","journal-title":"Dev. Biol."},{"key":"2021042606522907500_R44","first-page":"173","article-title":"Tissue interactions in embryonic mouse tooth germs","volume":"24","author":"Kollar","year":"1970","journal-title":"J. Embryol. Exp. Morphol."},{"key":"2021042606522907500_R45","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1101\/gad.1035602","article-title":"FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth organogenesis in Lef1\u2212\/\u2212 mice","volume":"16","author":"Kratochwil","year":"2002","journal-title":"Genes Dev."},{"key":"2021042606522907500_R46","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/dvg.20334","article-title":"A unique mouse strain expressing Cre recombinase for tissue-specific analysis of gene function in palate and kidney development","volume":"45","author":"Lan","year":"2007","journal-title":"Genesis"},{"key":"2021042606522907500_R47","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0925-4773(98)00072-0","article-title":"Developmental expression patterns of mouse sFRP genes encoding members of the secreted frizzled related protein family","volume":"75","author":"Leimeister","year":"1998","journal-title":"Mech. Dev."},{"key":"2021042606522907500_R48","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.bone.2006.03.017","article-title":"Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia","volume":"39","author":"Li","year":"2006","journal-title":"Bone"},{"key":"2021042606522907500_R49","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1086\/338450","article-title":"A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait","volume":"70","author":"Little","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"2021042606522907500_R50","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2021042606522907500_R51","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/dvdy.22047","article-title":"Expression of Axin2 indicates a role for canonical Wnt signaling in development of the crown and root during pre- and postnatal tooth development","volume":"239","author":"Lohi","year":"2010","journal-title":"Dev. Dyn."},{"key":"2021042606522907500_R52","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1101\/gr.3437105","article-title":"Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease","volume":"15","author":"Loots","year":"2005","journal-title":"Genome Res."},{"key":"2021042606522907500_R53","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.bone.2007.05.009","article-title":"Bone mass is inversely proportional to Dkk1 levels in mice","volume":"41","author":"MacDonald","year":"2007","journal-title":"Bone"},{"key":"2021042606522907500_R54","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1126\/science.1136370","article-title":"LRP6 mutation in a family with early coronary disease and metabolic risk factors","volume":"315","author":"Mani","year":"2007","journal-title":"Science"},{"key":"2021042606522907500_R55","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/35043051","article-title":"How cells read TGF-beta signals","volume":"1","author":"Massague","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042606522907500_R56","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1016\/j.febslet.2006.04.033","article-title":"The logic of TGFbeta signaling","volume":"580","author":"Massagu\u00e9","year":"2006","journal-title":"FEBS Lett."},{"key":"2021042606522907500_R57","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0003-9969(87)90055-0","article-title":"The induction of odontogenesis in non-dental mesenchyme combined with early murine mandibular arch epithelium","volume":"32","author":"Mina","year":"1987","journal-title":"Arch. Oral Biol."},{"key":"2021042606522907500_R58","doi-asserted-by":"crossref","first-page":"12919","DOI":"10.1073\/pnas.0609863104","article-title":"Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation","volume":"104","author":"Miquelajauregui","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042606522907500_R59","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S1534-5807(01)00041-7","article-title":"Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse","volume":"1","author":"Mukhopadhyay","year":"2001","journal-title":"Dev. Cell"},{"key":"2021042606522907500_R60","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1177\/00220345940730090601","article-title":"Induction of dentin formation on canine amputated pulp by recombinant human bone morphogenetic proteins (BMP)-2 and -4","volume":"73","author":"Nakashima","year":"1994","journal-title":"J. Dent. Res."},{"key":"2021042606522907500_R61","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00441-005-0136-6","article-title":"Gene expression of \u03b2-catenin is up-regulated in inner dental epithelium and enamel knots during molar tooth morphogenesis in the mouse","volume":"325","author":"Obara","year":"2006","journal-title":"Cell Tissue Res."},{"key":"2021042606522907500_R62","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":"Ohazama","year":"2008","journal-title":"PLoS ONE"},{"key":"2021042606522907500_R63","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.mod.2007.02.003","article-title":"Cell autonomous requirement for TGF-beta signaling during odontoblast differentiation and dentin matrix formation","volume":"124","author":"Oka","year":"2007","journal-title":"Mech. Dev."},{"key":"2021042606522907500_R64","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1182\/blood-2004-12-4940","article-title":"Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2","volume":"106","author":"Oshima","year":"2005","journal-title":"Blood"},{"key":"2021042606522907500_R65","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1525-142X.2005.05048.x","article-title":"Morphoregulation of teeth: modulating the number, size, shape and differentiation by tuning Bmp activity","volume":"7","author":"Plikus","year":"2005","journal-title":"Evol. Dev."},{"key":"2021042606522907500_R66","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1359\/jbmr.2003.18.10.1842","article-title":"BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop","volume":"18","author":"Rawadi","year":"2003","journal-title":"J. Bone Miner. Res."},{"key":"2021042606522907500_R67","first-page":"1","article-title":"Determinisms of odontogenesis","volume":"14","author":"Ruch","year":"1987","journal-title":"Revis. Biol. Celular."},{"key":"2021042606522907500_R68","first-page":"91","article-title":"Patterned distribution of differentiating dental cells: facts and hypotheses","volume":"18","author":"Ruch","year":"1990","journal-title":"J. Biol. Buccale"},{"key":"2021042606522907500_R69","first-page":"45","article-title":"Determinants of morphogenesis and cytodifferentiations of dental anloges in mice","volume":"1","author":"Ruch","year":"1973","journal-title":"J. Biol. Buccale"},{"key":"2021042606522907500_R70","first-page":"51","article-title":"Odontoblast differentiation","volume":"39","author":"Ruch","year":"1995","journal-title":"Int. J. Dev. Biol."},{"key":"2021042606522907500_R71","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/0092-8674(91)90308-L","article-title":"Proteoglycans as modulators of growth factor activities","volume":"64","author":"Ruoslahti","year":"1991","journal-title":"Cell"},{"key":"2021042606522907500_R72","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/0003-9969(94)90014-0","article-title":"The time-course of the induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1","volume":"39","author":"Rutherford","year":"1994","journal-title":"Arch. Oral Biol."},{"key":"2021042606522907500_R73","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0925-4773(99)00095-7","article-title":"Expression of Wnt signalling pathway genes during tooth development","volume":"85","author":"Sarkar","year":"1999","journal-title":"Mech. Dev."},{"key":"2021042606522907500_R74","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","article-title":"Mechanisms of TGF-beta signaling from cell membrane to the nucleus","volume":"113","author":"Shi","year":"2003","journal-title":"Cell"},{"key":"2021042606522907500_R75","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nrc1208","article-title":"Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer","volume":"3","author":"Siegel","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"2021042606522907500_R76","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/ar.1092400206","article-title":"Light and TEM study of nonregenerated and experimentally regenerated scales of Lepisosteus oculatus (Holostei) with particular attention to ganoine formation","volume":"240","author":"Sire","year":"1994","journal-title":"Anat. Rec."},{"key":"2021042606522907500_R77","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0003-9969(99)00131-4","article-title":"Stimulation of the rat dentine-pulp complex by bone morphogenetic protein-7 in vitro","volume":"45","author":"Sloan","year":"2000","journal-title":"Arch. Oral Biol."},{"key":"2021042606522907500_R78","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":"2021042606522907500_R79","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/dvdy.22106","article-title":"Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt\/beta-catenin signaling in the epithelial stem cells","volume":"239","author":"Suomalainen","year":"2010","journal-title":"Dev. Dyn."},{"key":"2021042606522907500_R80","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1038\/ncb1647","article-title":"A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation","volume":"9","author":"Takada","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"2021042606522907500_R81","first-page":"947","article-title":"Expression of the intermediate filament nestin during rodent tooth development","volume":"39","author":"Terling","year":"1995","journal-title":"Int. J. Dev. Biol."},{"key":"2021042606522907500_R82","first-page":"357","article-title":"The role of growth factors in determination and differentiation of the odontoblastic cell lineage","volume":"88","author":"Thesleff","year":"1992","journal-title":"Proc. Finn. Dent. Soc."},{"key":"2021042606522907500_R83","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/08959374010150010401","article-title":"Enamel knots as signaling centers linking tooth morphogenesis and odontoblast differentiation","volume":"15","author":"Thesleff","year":"2001","journal-title":"Adv. Dent. Res."},{"key":"2021042606522907500_R84","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/1097-0177(200007)218:3<480::AID-DVDY1011>3.0.CO;2-O","article-title":"Dissection of the odontoblast differentiation process in vitro by a combination of FGF1, FGF2, and TGFbeta1","volume":"218","author":"Unda","year":"2000","journal-title":"Dev. Dyn."},{"key":"2021042606522907500_R85","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1080\/03008200290000565","article-title":"TGF beta-1 downregulates DMP-1 and DSPP in odontoblasts","volume":"43","author":"Unterbrink","year":"2002","journal-title":"Connect. Tissue Res."},{"key":"2021042606522907500_R86","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1074\/jbc.M400524200","article-title":"Sclerostin inhibition of Wnt-3a-induced C3H10T1\/2 cell differentiation is indirect and mediated by bone morphogenetic proteins","volume":"280","author":"Winkler","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021042606522907500_R87","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/dvdy.20197","article-title":"PDGFR-alpha signaling is critical for tooth cusp and palate morphogenesis","volume":"232","author":"Xu","year":"2005","journal-title":"Dev. Dyn."},{"key":"2021042606522907500_R88","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ydbio.2006.05.014","article-title":"Cell autonomous requirement for Tgfbr2 in the disappearance of medial edge epithelium during palatal fusion","volume":"297","author":"Xu","year":"2006","journal-title":"Dev. Biol."},{"key":"2021042606522907500_R89","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.devcel.2008.06.004","article-title":"Ectodermal smad4 and p38 MAPK are functionally redundant in mediating TGF-beta\/BMP signaling during tooth and palate development","volume":"15","author":"Xu","year":"2008","journal-title":"Dev. Cell"},{"key":"2021042606522907500_R90","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1634\/stemcells.2006-0360","article-title":"Potential of dental mesenchymal cells in developing teeth","volume":"25","author":"Yamazaki","year":"2007","journal-title":"Stem Cells"},{"key":"2021042606522907500_R91","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/gene.10029","article-title":"Generation of Smad4\/Dpc4 conditional knockout mice","volume":"32","author":"Yang","year":"2002","journal-title":"Genesis"},{"key":"2021042606522907500_R92","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1634\/stemcells.2005-0544","article-title":"Bone morphogenetic protein signaling inhibits hair follicle anagen induction by restricting epithelial stem\/progenitor cell activation and expansion","volume":"24","author":"Zhang","year":"2006","journal-title":"Stem Cells"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/138\/10\/1977\/1475155\/1977.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/138\/10\/1977\/1475155\/1977.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T03:55:12Z","timestamp":1712375712000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/138\/10\/1977\/44381\/SMAD4-mediated-WNT-signaling-controls-the-fate-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,15]]},"references-count":92,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,5,15]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.061341","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2011,5,15]]}}}