{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:40:18Z","timestamp":1791322818978,"version":"4.3.1"},"reference-count":30,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2006,5,1]],"date-time":"2006-05-01T00:00:00Z","timestamp":1146441600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:p>Hertwig\u2019s epithelial root sheath (HERS) is important for tooth root formation, but the molecular basis for the signaling of root development remains uncertain. We hypothesized that Sonic hedgehog (Shh) signaling is involved in the HERS function, because it mediates epithelial-mesenchymal interactions during embryonic odontogenesis. We examined the gene expression patterns of Shh signaling in murine developing molar roots. Shh and Patched2 transcripts were identified in the HERS, whereas Patched1, Smoothened, and Gli1 were expressed in the proliferative dental mesenchyme in addition to the HERS. To confirm whether Shh signaling physiologically functions in vivo, we analyzed mesenchymal dysplasia ( mes) mice carrying an abnormal C-terminus of the PATCHED1 protein. In the mutant, cell proliferation was repressed around the HERS at 1 wk. Moreover, the molar eruption was disturbed, and all roots were shorter than those in control littermates at 4 wks. These results indicate that Shh signaling is important in tooth root development. Abbreviations used: BrdU, 5-bromo-2\u2032-deoxyuridine; HERS, Hertwig\u2019s epithelial root sheath; NFI-C\/CTF, nuclear factor Ic\/CAAT box transcription factor; PCNA, proliferating cell nuclear antigen; Ptc, patched; Shh, sonic hedgehog; Smo, smoothened.<\/jats:p>","DOI":"10.1177\/154405910608500506","type":"journal-article","created":{"date-parts":[[2009,1,8]],"date-time":"2009-01-08T19:39:42Z","timestamp":1231443582000},"page":"427-431","source":"Crossref","is-referenced-by-count":146,"title":["Sonic Hedgehog Signaling is Important in Tooth Root Development"],"prefix":"10.1177","volume":"85","author":[{"given":"M.","family":"Nakatomi","sequence":"first","affiliation":[{"name":"Section of Molecular Craniofacial Embryology,"},{"name":"Section of Cellular Physiological Chemistry, Department of Maxillofacial Biology, Graduate School, Tokyo Medical and Dental University, and"},{"name":"21st Century Center of Excellence (COE) Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Morita","sequence":"additional","affiliation":[{"name":"Section of Molecular Craniofacial Embryology,"},{"name":"Section of Cellular Physiological Chemistry, Department of Maxillofacial Biology, Graduate School, Tokyo Medical and Dental University, and"},{"name":"21st Century Center of Excellence (COE) Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Eto","sequence":"additional","affiliation":[{"name":"Section of Molecular Craniofacial Embryology,"},{"name":"Section of Cellular Physiological Chemistry, Department of Maxillofacial Biology, Graduate School, Tokyo Medical and Dental University, and"},{"name":"21st Century Center of Excellence (COE) Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.S.","family":"Ota","sequence":"additional","affiliation":[{"name":"Section of Molecular Craniofacial Embryology,"},{"name":"Section of Cellular Physiological Chemistry, Department of Maxillofacial Biology, Graduate School, Tokyo Medical and Dental University, and"},{"name":"21st Century Center of Excellence (COE) Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2006,5,1]]},"reference":[{"key":"BARNES-ETAL-2001","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.9.2214"},{"key":"BITGOOD-AND-MCMAHON-1995","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1995.0010"},{"key":"CHIANG-ETAL-1996","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"COBOURNE-ETAL-2001","doi-asserted-by":"publisher","DOI":"10.1177\/00220345010800110501"},{"key":"COHEN-2003","doi-asserted-by":"crossref","unstructured":"Cohen MM Jr (2003). The hedgehog signaling network. Am J Med Genet A 123:5\u201328.","DOI":"10.1002\/ajmg.a.20495"},{"key":"DASSULE-AND-MCMAHON-1998","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.8992"},{"key":"DASSULE-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Dassule HR, Lewis P, Bei M, Maas R, McMahon AP (2000). Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127:4775\u20134785.","DOI":"10.1242\/dev.127.22.4775"},{"key":"FUJIWARA-ETAL-2005","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-004-1065-5"},{"key":"GOODRICH-ETAL-1997","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5329.1109"},{"key":"GRITLI-LINDE-ETAL-2002","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00100"},{"key":"HAHN-ETAL-1996","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81268-4"},{"key":"HARDCASTLE-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Hardcastle Z, Mo R, Hui CC, Sharpe PT (1998). The Shh signalling pathway in tooth development: defects in\n                      Gli2\n                      and\n                      Gli3\n                      mutants. Development 125:2803\u20132811.","DOI":"10.1242\/dev.125.15.2803"},{"key":"HARDCASTLE-ETAL-1999","unstructured":"Hardcastle Z, Hui CC, Sharpe PT (1999). The Shh signalling pathway in early tooth development. Cell Mol Biol\n                      (Noisy-le-grand)\n                      45:567\u2013578."},{"key":"INGHAM-AND-MCMAHON-2001","doi-asserted-by":"publisher","DOI":"10.1101\/gad.938601"},{"key":"JERNVALL-AND-THESLEFF-2000","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00322-6"},{"key":"MAKINO-ETAL-2001","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0419"},{"key":"MARIGO-ETAL-1996A","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0300"},{"key":"MARIGO-ETAL-1996B","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.4.1225"},{"key":"MCMAHON-ETAL-2003","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(03)53002-2"},{"key":"MILENKOVIC-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Milenkovi\u0107 L, Goodrich LV, Higgins KM, Scott MP (1999). Mouse\n                      patched1\n                      controls body size determination and limb patterning. Development 126:4431\u20134440.","DOI":"10.1242\/dev.126.20.4431"},{"key":"MOTOYAMA-ETAL-1998","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-104"},{"key":"STEELE-PERKINS-ETAL-2003","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.3.1075-1084.2003"},{"key":"SWEET-ETAL-1996","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a022981"},{"key":"TEN-CATE-1996","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.1996.tb00204.x"},{"key":"TICKLE-2003","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00095-9"},{"key":"TUCKER-AND-SHARPE-2004","doi-asserted-by":"crossref","unstructured":"Tucker A, Sharpe P (2004). The cutting-edge of mammalian development; how the embryo makes teeth. Nat Rev Genet 5:499\u2013508.","DOI":"10.1038\/nrg1380"},{"key":"VAAHTOKARI-ETAL-1996","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(95)00459-9"},{"key":"XU-AND-WILKINSON-1999","doi-asserted-by":"crossref","unstructured":"Xu Q, Wilkinson DG (1999).\n                      In situ\n                      hybridization of mRNA with hapten labelled probes. In:\n                      In situ\n                      hybridization: a practical approach. 2nd ed. Wilkinson DG, editor. Oxford: Oxford University Press, pp. 87\u2013106.","DOI":"10.1093\/oso\/9780199636594.003.0004"},{"key":"YAMASHIRO-ETAL-2003","doi-asserted-by":"publisher","DOI":"10.1177\/154405910308200305"},{"key":"ZHANG-ETAL-2001","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00385-3"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/154405910608500506","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/154405910608500506","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/154405910608500506","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:02:47Z","timestamp":1777496567000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/154405910608500506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006,5]]}},"alternative-id":["10.1177\/154405910608500506"],"URL":"https:\/\/doi.org\/10.1177\/154405910608500506","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,5]]}}}