{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:17:10Z","timestamp":1753892230763,"version":"3.41.2"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["1R56 DE026464-01A1"],"award-info":[{"award-number":["1R56 DE026464-01A1"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>The secondary palate forms from two lateral primordia called the palatal shelves which form a contact in the midline, become adherent at the fusing interface (medial edge epithelia, MEE) and subsequently fuse. The gene encoding transforming growth factor-\u00df3 (<jats:italic>Tgfb3<\/jats:italic>) is strongly and specifically expressed in MEE cells. Our previous study suggested that <jats:italic>Tgfb3<\/jats:italic> expression is controlled via upstream cis-regulatory elements in and around the neighboring <jats:italic>Ift43<\/jats:italic> gene. Another study suggested that the canonical Wnt signaling via \u00df-Catenin is responsible for the MEE-specific <jats:italic>Tgfb3<\/jats:italic> gene expression, since deletion of the <jats:italic>Ctnnb1<\/jats:italic> gene by a commonly used Keratin 14-Cre (<jats:italic>K14Cre<\/jats:italic>) mouse line almost completely abolished <jats:italic>Tgfb3<\/jats:italic> expression in the MEE resulting in cleft palate. Here, we wanted to analyze whether <jats:italic>Tcf\/Lef<\/jats:italic> consensus binding sites located in the previously identified regions of the <jats:italic>Ift43<\/jats:italic> gene are responsible for the spatiotemporal control of <jats:italic>Tgfb3<\/jats:italic> expression during palatogenesis. We show that contrary to the previous report, deletion of the <jats:italic>Ctnnb1<\/jats:italic> gene in basal MEE cells by the <jats:italic>K14Cre<\/jats:italic> driver (the same <jats:italic>K14Cre<\/jats:italic> mouse line was used as in the previous study referenced above) does not affect the MEE-specific <jats:italic>Tgfb3<\/jats:italic> expression or TGF\u00df3-dependent palatal epithelial fusion. All mutant embryos showed a lack of palatal rugae accompanied by other craniofacial defects, e.g., a narrow snout and a small upper lip, while only a small subset (&amp;lt;5%) of <jats:italic>Ctnnb1<\/jats:italic> mutants displayed a cleft palate. Moreover, the <jats:italic>K14Cre:Ctnnb1<\/jats:italic> embryos showed reduced levels and altered patterns of <jats:italic>Shh<\/jats:italic> expression. Our present data imply that epithelial \u00df-catenin may not be required for MEE-specific <jats:italic>Tgfb3<\/jats:italic> expression or palatal epithelial fusion.<\/jats:p>","DOI":"10.3389\/fphys.2023.704406","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T05:42:59Z","timestamp":1683870179000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Canonical Wnt signaling is not required for Tgfb3 expression in the basal medial edge epithelium during palatogenesis"],"prefix":"10.3389","volume":"14","author":[{"given":"Ghazi-Abdullah","family":"Saroya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Siismets","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Panaretos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Rice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengji J.","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesa","family":"Kaartinen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1242\/dev.01125","article-title":"Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development","volume":"131","author":"Andl","year":"2004","journal-title":"Development"},{"key":"B2","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.ydbio.2010.12.028","article-title":"Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation","volume":"350","author":"Baek","year":"2011","journal-title":"Dev. Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1242\/dev.128.8.1253","article-title":"Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development","volume":"128","author":"Brault","year":"2001","journal-title":"Development"},{"key":"B4","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1242\/dev.067082","article-title":"Palatogenesis: Morphogenetic and molecular mechanisms of secondary palate development","volume":"139","author":"Bush","year":"2012","journal-title":"Development"},{"key":"B5","doi-asserted-by":"publisher","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":"B6","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.ydbio.2010.12.021","article-title":"Epithelial Wnt\/\u03b2-catenin signaling regulates palatal shelf fusion through regulation of Tgf\u03b23 expression","volume":"350","author":"He","year":"2011","journal-title":"Dev. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.ydbio.2015.02.010","article-title":"Integration of comprehensive 3D microCT and signaling analysis reveals differential regulatory mechanisms of craniofacial bone development","volume":"400","author":"Ho","year":"2015","journal-title":"Dev. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/jcp.24856","article-title":"TGF\u03b23 regulates periderm removal through \u0394Np63 in the developing palate","volume":"230","author":"Hu","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/ng1295-415","article-title":"Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction","volume":"11","author":"Kaartinen","year":"1995","journal-title":"Nat. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e1002122","DOI":"10.1371\/journal.pbio.1002122","article-title":"Convergence and extrusion are required for normal fusion of the Mammalian secondary palate","volume":"13","author":"Kim","year":"2015","journal-title":"PLoS Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/bs.ctdb.2015.07.002","article-title":"Cellular and molecular mechanisms of palatogenesis","volume":"115","author":"Lan","year":"2015","journal-title":"Curr. Top. Dev. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/wsbm.1265","article-title":"Signaling networks in palate development","volume":"6","author":"Lane","year":"2014","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3389\/fphys.2014.00258","article-title":"Control elements targeting Tgfb3 expression to the palatal epithelium are located intergenically and in introns of the upstream Ift43 gene","volume":"5","author":"Lane","year":"2014","journal-title":"Front. Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s00418-011-0870-7","article-title":"Shh signaling is essential for rugae morphogenesis in mice","volume":"136","author":"Lee","year":"2011","journal-title":"Histochem Cell. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ydbio.2011.05.002","article-title":"The inductive role of Wnt-beta-Catenin signaling in the formation of oral apparatus","volume":"356","author":"Lin","year":"2011","journal-title":"Dev. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/002215540104900101","article-title":"Sensitive nonradioactive detection of mRNA in tissue sections: Novel application of the whole-mount in situ hybridization protocol","volume":"49","author":"Moorman","year":"2001","journal-title":"JHistochemCytochem"},{"key":"B17","doi-asserted-by":"publisher","first-page":"pdb.prot4726","DOI":"10.1101\/pdb.prot4726","article-title":"Staining frozen mouse embryo sections for {beta}-Galactosidase (lacZ) activity","volume":"2007","author":"Nagy","year":"2007","journal-title":"CSH Protoc."},{"key":"B18","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/0012-1606(90)90401-4","article-title":"Differential expression of genes encoding TGFs beta 1, beta 2, and beta 3 during murine palate formation","volume":"141","author":"Pelton","year":"1990","journal-title":"Dev. Biol."},{"key":"B19","doi-asserted-by":"publisher","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":"B20","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.modgep.2005.06.005","article-title":"Expression patterns of Hedgehog signalling pathway members during mouse palate development","volume":"6","author":"Rice","year":"2006","journal-title":"Gene Expr. Patterns"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1172\/JCI20384","article-title":"Disruption of Fgf10\/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate","volume":"113","author":"Rice","year":"2004","journal-title":"J. Clin. Invest."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e1006828","DOI":"10.1371\/journal.pgen.1006828","article-title":"p63 exerts spatio-temporal control of palatal epithelial cell fate to prevent cleft palate","volume":"13","author":"Richardson","year":"2017","journal-title":"PLoS Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"14300","DOI":"10.1038\/ncomms14300","article-title":"Evolution of Shh endoderm enhancers during morphological transition from ventral lungs to dorsal gas bladder","volume":"8","author":"Sagai","year":"2017","journal-title":"Nat. Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"pdb.prot094029","DOI":"10.1101\/pdb.prot094029","article-title":"DAPI staining of whole-mount mouse embryos or fetal organs","volume":"2018","author":"Sandell","year":"2018","journal-title":"Cold Spring Harb. Protoc."},{"key":"B25","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1177\/00220345221146454","article-title":"Periderm fate during palatogenesis: TGF-\u03b2 and periderm dedifferentiation","volume":"102","author":"Saroya","year":"2023","journal-title":"J. Dent. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1177\/0022034518758642","article-title":"Upstream enhancer elements of Shh regulate oral and dental patterning","volume":"97","author":"Seo","year":"2018","journal-title":"J. Dent. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"dev200181","DOI":"10.1242\/dev.200181","article-title":"A unique form of collective epithelial migration is crucial for tissue fusion in the secondary palate and can overcome loss of epithelial apoptosis","volume":"149","author":"Teng","year":"2022","journal-title":"Development"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1093\/hmg\/ddq547","article-title":"MSX1 and TGF-beta3 are novel target genes functionally regulated by FOXE1","volume":"20","author":"Venza","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/j.1365-2443.2012.01601.x","article-title":"Periderm cells covering palatal shelves have tight junctions and their desquamation reduces the polarity of palatal shelf epithelial cells in palatogenesis","volume":"17","author":"Yoshida","year":"2012","journal-title":"Genes. cells."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.704406\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T05:43:02Z","timestamp":1683870182000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.704406\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,12]]},"references-count":29,"alternative-id":["10.3389\/fphys.2023.704406"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2023.704406","relation":{},"ISSN":["1664-042X"],"issn-type":[{"type":"electronic","value":"1664-042X"}],"subject":[],"published":{"date-parts":[[2023,5,12]]},"article-number":"704406"}}