{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:36:56Z","timestamp":1790177816279,"version":"4.1.0"},"reference-count":114,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T00:00:00Z","timestamp":1542585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Signaling by transforming growth factor (TGF)-\u03b2 plays an important role in development, including in palatogenesis. The dynamic morphological process of palatal fusion occurs to achieve separation of the nasal and oral cavities. Critically and specifically important in palatal fusion are the medial edge epithelial (MEE) cells, which are initially present at the palatal midline seam and over the course of the palate fusion process are lost from the seam, due to cell migration, epithelial-mesenchymal transition (EMT), and\/or programed cell death. In order to define the role of TGF-\u03b2 signaling during this process, several approaches have been utilized, including a small interfering RNA (siRNA) strategy targeting TGF-\u03b2 receptors in an organ culture context, the use of genetically engineered mice, such as Wnt1-cre\/R26R double transgenic mice, and a cell fate tracing through utilization of cell lineage markers. These approaches have permitted investigators to distinguish some specific traits of well-defined cell populations throughout the palatogenic events. In this paper, we summarize the current understanding on the role of TGF-\u03b2 signaling, and specifically its association with MEE cell fate during palatal fusion. TGF-\u03b2 is highly regulated both temporally and spatially, with TGF-\u03b23 and Smad2 being the preferentially expressed signaling molecules in the critical cells of the fusion processes. Interestingly, the accessory receptor, TGF-\u03b2 type 3 receptor, is also critical for palatal fusion, with evidence for its significance provided by Cre-lox systems and siRNA approaches. This suggests the high demand of ligand for this fine-tuned signaling process. We discuss the new insights in the fate of MEE cells in the midline epithelial seam (MES) during the palate fusion process, with a particular focus on the role of TGF-\u03b2 signaling.<\/jats:p>","DOI":"10.3390\/ijms19113638","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T11:23:27Z","timestamp":1542799407000},"page":"3638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["TGF-\u03b2 Signaling and the Epithelial-Mesenchymal Transition during Palatal Fusion"],"prefix":"10.3390","volume":"19","author":[{"given":"Akira","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"F. Shuler","sequence":"additional","affiliation":[{"name":"Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander O. D.","family":"Gulka","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Center for Cancer Research, Charlestown, MA 02129-2020, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Hanai","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Center for Cancer Research, Charlestown, MA 02129-2020, USA"},{"name":"Harvard Medical School, Department of Medicine, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(09)60695-4","article-title":"Cleft lip and palate","volume":"374","author":"Mossey","year":"2009","journal-title":"Lancet"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.ydbio.2005.07.027","article-title":"Fate-mapping of the epithelial seam during palatal fusion rules out epithelial-mesenchymal transformation","volume":"285","author":"Hallberg","year":"2005","journal-title":"Dev. 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