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In the present study, we report that during early taste papilla development in mouse embryos, bone morphogenetic protein (BMP) signaling mediated by type 1 receptor ALK3 in the tongue mesenchyme is required for epithelial Wnt\/\u03b2-catenin activity and taste papilla differentiation. Mesenchyme-specific knockout (cKO) of Alk3 using Wnt1-Cre and Sox10-Cre resulted in an absence of taste papillae at E12.0. Biochemical and cell differentiation analyses demonstrated that mesenchymal ALK3-BMP signaling governed the production of previously unappreciated secretory proteins, i.e. it suppressed those that inhibit and facilitated those that promote taste papilla differentiation. Bulk RNA-sequencing analysis revealed many more differentially expressed genes (DEGs) in the tongue epithelium than in the mesenchyme in Alk3 cKO versus control. Moreover, we detected downregulated epithelial Wnt\/\u03b2-catenin signaling and found that taste papilla development in the Alk3 cKO was rescued by the GSK3\u03b2 inhibitor LiCl, but not by Wnt3a. Our findings demonstrate for the first time the requirement of tongue mesenchyme in taste papilla cell differentiation.<\/jats:p>","DOI":"10.1242\/dev.201838","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T03:49:13Z","timestamp":1694144953000},"source":"Crossref","is-referenced-by-count":9,"title":["Taste papilla cell differentiation requires the regulation of secretory protein production by ALK3-BMP signaling in the tongue mesenchyme"],"prefix":"10.1242","volume":"150","author":[{"given":"Mohamed","family":"Ishan","sequence":"first","affiliation":[{"name":"Regenerative Bioscience Center 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"},{"name":"College of Agricultural and Environmental Sciences, University of Georgia 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghou","family":"Wang","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"},{"name":"College of Agricultural and Environmental Sciences, University of Georgia 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia 2 , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yao","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"},{"name":"College of Agricultural and Environmental Sciences, University of Georgia 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Stice","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"},{"name":"College of Agricultural and Environmental Sciences, University of Georgia 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance","family":"Wells","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, University of Georgia 2 , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Mishina","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of Michigan 3 Department of Biologic and Materials Sciences , , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-9869","authenticated-orcid":false,"given":"Hong-Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"},{"name":"College of Agricultural and Environmental Sciences, University of Georgia 1 , Department of Animal and Dairy Science , , Athens, GA 30602 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"2023092512270861000_DEV201838C1","doi-asserted-by":"publisher","first-page":"3620","DOI":"10.1242\/dev.120394","article-title":"Progress and renewal in gustation: new insights into taste bud development","volume":"142","author":"Barlow","year":"2015","journal-title":"Development"},{"key":"2023092512270861000_DEV201838C2","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1242\/dev.056929","article-title":"Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis","volume":"138","author":"Barron","year":"2011","journal-title":"Development"},{"key":"2023092512270861000_DEV201838C3","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1242\/dev.030544","article-title":"Follistatin modulates a BMP autoregulatory loop to control the size and patterning of sensory domains in the developing tongue","volume":"136","author":"Beites","year":"2009","journal-title":"Development"},{"key":"2023092512270861000_DEV201838C4","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3389\/fcell.2017.00047","article-title":"A novel role for the BMP antagonist noggin in sensitizing cells to non-canonical Wnt-5a\/Ror2\/disheveled pathway activation","volume":"5","author":"Bernatik","year":"2017","journal-title":"Front. 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