{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:25:28Z","timestamp":1791804328200,"version":"4.3.4"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Normal fusion of the upper lip and primary palate is a complex process involving a series of characteristic and orderly regulated cellular events. Cleft lip with or without palate (CL\/P), one of the most common congenital malformations, may be induced by abnormalities in any of these events. However, less is known about the precise regulatory process in the fusion of the upper lip and primary palate.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Lambdoidal junction tissues of mice from embryonic days 10.5, 11.5, and 12.5\u2014 three key fusion stages\u2014were acquired for RNA sequencing.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Gene expression profiles in distinct fusion stages of mice were identified. Some of the differentially expressed genes (DEGs) have been reported to affect upper lip and primary palate development. However, other DEGs, such as <jats:italic>Krt5<\/jats:italic>, <jats:italic>Pax1<\/jats:italic>, <jats:italic>Ambn<\/jats:italic>, <jats:italic>Hey2<\/jats:italic>, and <jats:italic>Tnmd<\/jats:italic>, have not previously been investigated. Gene set enrichment analysis (GSEA) of these DEGs revealed the sequential intensification of Wnt, PI3K-Akt, MAPK, Hippo, and TGF-beta signaling pathways and identified relatively highly expressed genes including <jats:italic>Tnn, Wnt3a<\/jats:italic>, and <jats:italic>Wnt16<\/jats:italic>. We also observed substantial alternative splicing events during the fusion of the upper lip and primary palate and identified potentially important genes including <jats:italic>Gtpbp8, Armcx1, Tle3<\/jats:italic>, and <jats:italic>Numa1<\/jats:italic>. Protein-protein interaction (PPI) network analysis identified a series of hub genes, including <jats:italic>Col1a2, Fos, Bmp2, Shh, Col1a1, Wnt3a, Anxa1, Gem<\/jats:italic>, etc.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Overall, the results of this study provided a comprehensive analysis of the development of the upper lip and primary palate. Our work provides insight into future studies of normal upper lip and primary palate development and the etiology of CL\/P.<\/jats:p>","DOI":"10.3389\/fgene.2022.1039850","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T13:59:57Z","timestamp":1673013597000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptomic analysis of the upper lip and primary palate development in mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Sini","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuo","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningbei","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nrm.2017.27","article-title":"Alternative splicing as a regulator of development and tissue identity","volume":"18","author":"Baralle","year":"2017","journal-title":"Nat. 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