{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:43:31Z","timestamp":1760402611715,"version":"build-2065373602"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008317","name":"American Cleft Palate-Craniofacial Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008317","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE019471","DE019471\u2010ARRA"],"award-info":[{"award-number":["DE019471","DE019471\u2010ARRA"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the strides made in understanding the complex network of key regulatory genes and cellular processes that drive palate morphogenesis, patients suffering from these conditions face treatment options that are limited to complex surgeries and multidisciplinary care throughout life. Hence, a better understanding of how molecular interactions drive palatal growth and fusion is critical for the development of treatment and preventive strategies for cleft palates in humans. Our previous work demonstrated that <jats:italic>Pax9<\/jats:italic>\u2010dependent Wnt signaling is critical for the growth and fusion of palatal shelves. We showed that controlled intravenous delivery of small molecule Wnt agonists specifically blocks the action of Dkks (inhibitors of Wnt signaling) and corrects secondary palatal clefts in <jats:italic>Pax9<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. While these data underscore the importance of the functional upstream relationship of <jats:italic>Pax9<\/jats:italic> to the Wnt pathway, not much is known about how the genetic nature of <jats:italic>Pax9's<\/jats:italic> interactions in vivo and how it modulates the actions of these downstream effectors during palate formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we show that the genetic reduction of <jats:italic>Dkk1<\/jats:italic> during palatogenesis corrected secondary palatal clefts in <jats:italic>Pax9<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice with restoration of Wnt signaling activities. In contrast, genetically induced overexpression of <jats:italic>Dkk1<\/jats:italic> mice phenocopied the defects in tooth and palate development visible in <jats:italic>Pax9<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> strains. Results of ChIP\u2010qPCR assays showed that Pax9 can bind to regions near the transcription start sites of <jats:italic>Dkk1<\/jats:italic> and <jats:italic>Dkk2<\/jats:italic> as well as the intergenic region of <jats:italic>Wnt9b<\/jats:italic> and <jats:italic>Wnt3<\/jats:italic> ligands that are downregulated in <jats:italic>Pax9<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> palates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these data suggest that the molecular mechanisms underlying <jats:italic>Pax9's<\/jats:italic> role in modulating Wnt signaling activity likely involve the inhibition of Dkk expression and the control of Wnt ligands during palatogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.189","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T04:55:21Z","timestamp":1589172921000},"page":"1274-1284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pax9's dual roles in modulating Wnt signaling during murine palatogenesis"],"prefix":"10.1002","volume":"249","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-4291","authenticated-orcid":false,"given":"Shihai","family":"Jia","sequence":"first","affiliation":[{"name":"School of Dentistry, School of Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Dentistry, School of Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rena N.","family":"D'Souza","sequence":"additional","affiliation":[{"name":"School of Dentistry, School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Department of Neurobiology &amp; Anatomy, School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Department of Pathology, School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Department of Surgery, School of Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3074"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.10.016"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2015.07.006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.158048"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.037051"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1597\/15-029"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31381"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cps.2013.12.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00067"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.4331\/wjbc.v6.i3.121"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000337619"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.05.016"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.08.005"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.075796"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.052001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2015.11.028"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.12.021"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05557"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025847"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.07.015"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.157750"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517719865"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.081927"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.08.014"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.099028"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517726073"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714322"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.03.012"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0434590100"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199905)215:1<45::AID-DVDY5>3.0.CO;2-5"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650080914"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01175"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.416545"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.07.008"}],"container-title":["Developmental Dynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvdy.189","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.189","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dvdy.189","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:54:42Z","timestamp":1760363682000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/dvdy.189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,4]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1002\/dvdy.189"],"URL":"https:\/\/doi.org\/10.1002\/dvdy.189","archive":["Portico"],"relation":{},"ISSN":["1058-8388","1097-0177"],"issn-type":[{"type":"print","value":"1058-8388"},{"type":"electronic","value":"1097-0177"}],"subject":[],"published":{"date-parts":[[2020,8,4]]},"assertion":[{"value":"2019-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}