{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:43:54Z","timestamp":1780490634703,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["20K18463"],"award-info":[{"award-number":["20K18463"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["21K09820"],"award-info":[{"award-number":["21K09820"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["2020 A and 2021 A"],"award-info":[{"award-number":["2020 A and 2021 A"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Meikai University Miyata Research","award":["20K18463"],"award-info":[{"award-number":["20K18463"]}]},{"name":"Meikai University Miyata Research","award":["21K09820"],"award-info":[{"award-number":["21K09820"]}]},{"name":"Meikai University Miyata Research","award":["2020 A and 2021 A"],"award-info":[{"award-number":["2020 A and 2021 A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The mammalian secondary palate is formed through complex developmental processes: growth, elevation, and fusion. Although it is known that the palatal elevation pattern changes along the anterior\u2013posterior axis, it is unclear what molecules are expressed and whether their locations change before and after elevation. We examined the expression regions of molecules associated with palatal shelf elevation (Pax9, Osr2, and Tgf\u03b23) and tissue deformation (F-actin, E-cadherin, and Ki67) using immunohistochemistry and RT\u2013PCR in mouse embryos at E13.5 (before elevation) and E14.5 (after elevation). Pax9 was expressed at significantly higher levels in the lingual\/nasal region in the anterior and middle parts, as well as in the buccal\/oral region in the posterior part at E13.5. At E14.5, Pax9 was expressed at significantly higher levels in both the lingual\/nasal and buccal\/oral regions in the anterior and middle parts and the buccal\/oral regions in the posterior part. Osr2 was expressed at significantly higher levels in the buccal\/oral region in all parts at E13.5 and was more strongly expressed at E13.5 than at E14.5 in all regions. No spatiotemporal changes were found in the other molecules. These results suggested that Pax9 and Osr2 are critical molecules leading to differences in the elevation pattern in palatogenesis.<\/jats:p>","DOI":"10.3390\/ijms23095160","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T13:10:26Z","timestamp":1651756226000},"page":"5160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Spatiotemporal Gene Expression Regions along the Anterior\u2013Posterior Axis in Mouse Embryos before and after Palatal Elevation"],"prefix":"10.3390","volume":"23","author":[{"given":"Arata","family":"Nagasaka","sequence":"first","affiliation":[{"name":"Division of Histology\/Anatomy, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado 350-0283, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Sakiyama","sequence":"additional","affiliation":[{"name":"Division of Histology\/Anatomy, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado 350-0283, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Bando","sequence":"additional","affiliation":[{"name":"Division of Histology\/Anatomy, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado 350-0283, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9683-6678","authenticated-orcid":false,"given":"Masahito","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Tokyo Dental College, 2-9-18, Kandamisaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4632-9736","authenticated-orcid":false,"given":"Shinichi","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Tokyo Dental College, 2-9-18, Kandamisaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4654-3903","authenticated-orcid":false,"given":"Osamu","family":"Amano","sequence":"additional","affiliation":[{"name":"Division of Histology\/Anatomy, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado 350-0283, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"620735","DOI":"10.3389\/fcell.2020.620735","article-title":"insights into the complexity of craniofacial development from a cellular perspective","volume":"8","author":"Kaucka","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1083\/jcb.201402093","article-title":"In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity","volume":"206","author":"Kuriyama","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1600060","DOI":"10.1126\/sciadv.1600060","article-title":"Analysis of neural crest-derived clones reveals novel aspects of facial development","volume":"2","author":"Kaucka","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ydbio.2010.11.012","article-title":"Ectodermal Wnt\/\u03b2-catenin signaling shapes the mouse face","volume":"349","author":"Reid","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Abramyan, J. (2019). Hedgehog signaling and embryonic craniofacial disorders. J. Dev. Biol., 7.","DOI":"10.3390\/jdb7020009"},{"key":"ref_6","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":"Peters","year":"1998","journal-title":"Genes Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"188561","DOI":"10.1016\/j.bbcan.2021.188561","article-title":"The clinical significance and correlative signaling pathways of paired box gene 9 in development and carcinogenesis","volume":"1876","author":"Bhol","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrg2933","article-title":"Cleft lip and palate: Understanding genetic and environmental influences","volume":"12","author":"Dixon","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1242\/dev.103.Supplement.41","article-title":"Palate development","volume":"103","author":"Ferguson","year":"1988","journal-title":"Development"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1177\/0022034518811861","article-title":"The function and regulatory network of Pax9 gene in palate development","volume":"98","author":"Li","year":"2019","journal-title":"J. Dent. Res."},{"key":"ref_11","first-page":"27","article-title":"Immunolocalization of heat shock protein 25 (Hsp25) in developing secondary palate pf mouse embryos","volume":"24","author":"Yamada","year":"2014","journal-title":"Pediatr. Oral Maxillofac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1177\/0022034517703580","article-title":"Molecular and cellular mechanisms of palate development","volume":"96","author":"Li","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3389\/fcell.2019.00340","article-title":"Extracellular matrix composition and remodeling: Current perspectives on secondary palate formation, cleft lip\/palate, and palatal reconstruction","volume":"7","author":"Paiva","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/ng1295-409","article-title":"Transforming growth factor-beta 3 is required for secondary palate fusion","volume":"11","author":"Proetzel","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1242\/dev.01175","article-title":"Odd-skipped related 2 (Osr2) encodes a key intrinsic regulator of secondary palate growth and morphogenesis","volume":"131","author":"Lan","year":"2004","journal-title":"Development"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1002\/dvdy.22339","article-title":"Mesenchymal cell remodeling during mouse secondary palate reorientation","volume":"239","author":"Jin","year":"2010","journal-title":"Dev. Dyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1002\/dvdy.22670","article-title":"Histomorphological study of palatal shelf elevation during murine secondary palate formation","volume":"240","author":"Yu","year":"2011","journal-title":"Dev. Dyn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1242\/dev.099028","article-title":"Pax9 regulates a molecular network involving Bmp4, Fgf10, Shh signaling and the Osr2 transcription factor to control palate morphogenesis","volume":"140","author":"Zhou","year":"2013","journal-title":"Development"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.archoralbio.2006.09.012","article-title":"Temporal and spatial expression of Pax9 and sonic hedgehog during development of normal mouse palates and cleft palates in TGF-beta3 null embryos","volume":"52","author":"Sasaki","year":"2007","journal-title":"Arch. Oral Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1242\/dev.109.3.585","article-title":"Differential expression of TGF beta isoforms in murine palatogenesis","volume":"109","author":"Fitzpatrick","year":"1990","journal-title":"Development"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/ng0493-292","article-title":"Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9","volume":"3","author":"Stapleton","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0925-4773(01)00457-9","article-title":"Osr2, a new mouse gene related to Drosophila odd-skipped, exhibits dynamic expression patterns during craniofacial, limb, and kidney development","volume":"107","author":"Lan","year":"2001","journal-title":"Mech. Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ydbio.2009.01.008","article-title":"Functional equivalence of the zinc finger transcription factors Osr1 and Osr2 in mouse development","volume":"328","author":"Gao","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.dci.2003.09.007","article-title":"Transforming growth factor-beta-related proteins: An ancestral and widespread superfamily of cytokines in metazoans","volume":"28","author":"Herpin","year":"2004","journal-title":"Dev. Comp. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1242\/dev.102.4.639","article-title":"The cadherins: Cell-cell adhesion molecules controlling animal morphogenesis","volume":"102","author":"Takeichi","year":"1988","journal-title":"Development"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/joa.12425","article-title":"Mapping cellular processes in the mesenchyme during palatal development in the absence of Tbx1 reveals complex proliferation changes and perturbed cell packing and polarity","volume":"228","author":"Brock","year":"2016","journal-title":"J. Anat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jsbmb.2017.02.005","article-title":"Class 3 semaphorins are transcriptionally regulated by 1,25(OH)2D3 in osteoblasts","volume":"173","author":"Kriebizsch","year":"2017","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1177\/0022034517719749","article-title":"Identification of Osr2 transcriptional target genes inn palate development","volume":"96","author":"Fu","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.semcdb.2017.08.021","article-title":"Periderm: Life-cycle and function during orofacial and epidermal development","volume":"91","author":"Hammond","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1242\/dev.089615","article-title":"Smad4-Irf6 genetic interaction and TGF\u03b2-mediated IRF6 signaling cascade are crucial for palatal fusion in mice","volume":"140","author":"Iwata","year":"2013","journal-title":"Development"},{"key":"ref_31","first-page":"2840","article-title":"Interferon regulatory factor 6 regulates keratinocyte migration","volume":"127","author":"Biggs","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3389\/fphys.2016.00392","article-title":"Mesenchymal remodeling during palatal shelf elevation revealed by extracellular matrix and F-actin expression patterns","volume":"7","author":"Chiquet","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/15476278.2020.1735239","article-title":"Extracellular matrix remodeling during palate development","volume":"16","author":"Wang","year":"2020","journal-title":"Organogenesis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41368-020-00110-4","article-title":"FACEs of mechanical regulation in the morphogenesis of craniofacial structures","volume":"13","author":"Du","year":"2021","journal-title":"Int. J. Oral Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.cell.2013.05.008","article-title":"Forces in tissue morphogenesis and patterning","volume":"153","author":"Heisenberg","year":"2013","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ceb.2020.05.004","article-title":"Forces to communicate: Integration of mechanical and biochemical signaling in morphogenesis","volume":"66","author":"Kindberg","year":"2020","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1083\/jcb.201001149","article-title":"Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin \u2161-dependent manner","volume":"189","author":"Shi","year":"2010","journal-title":"J. Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/5160\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:31Z","timestamp":1760137591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/5160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijms23095160"],"URL":"https:\/\/doi.org\/10.3390\/ijms23095160","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,5]]}}}