Wnt signaling interacts with Shh to regulate taste papilla development
Wnt and Shh signaling pathways are critical for the development and maturation of many epithelial tissues. Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we re...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2007-02, Vol.104 (7), p.2253-2258 |
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| creator | Iwatsuki, Ken Liu, Hong-Xiang Grónder, Albert Singer, Meredith A Lane, Timothy F Grosschedl, Rudolf Mistretta, Charlotte M Margolskee, Robert F |
| description | Wnt and Shh signaling pathways are critical for the development and maturation of many epithelial tissues. Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expression in fungiform papillae and formation of normal mature fungiform papillae depend on signaling through Wnt and β-catenin. We observed that during fungiform papilla formation in mice, Shh and components of the Wnt/β-catenin signaling pathway are expressed together in the developing placode. The elimination of Wnt/β-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression. In addition, the size and number of fungiform papillae were greatly reduced in Lef1 knockout mice. By examining embryonic mouse tongues in culture we determined that activation of Wnt/β-catenin signaling up-regulates Shh expression. We observed that blocking Shh signaling in cultured tongue explants enhanced papillae formation and was accompanied by an up-regulation of Wnt/β-catenin signaling, indicating that Shh inhibits the Wnt/β-catenin pathway. Exogenously added Shh suppressed expression of endogenous Shh and inhibited Wnt/β-catenin signaling (assessed in TOPGAL mice), further implicating Shh as an inhibitor of the Wnt/β-catenin pathway. Our observations indicate that Wnt/β-catenin signaling and interactions between the Wnt and Shh pathways play essential roles in the development of fungiform papillae. |
| doi_str_mv | 10.1073/pnas.0607399104 |
| format | Article |
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Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expression in fungiform papillae and formation of normal mature fungiform papillae depend on signaling through Wnt and β-catenin. We observed that during fungiform papilla formation in mice, Shh and components of the Wnt/β-catenin signaling pathway are expressed together in the developing placode. The elimination of Wnt/β-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression. In addition, the size and number of fungiform papillae were greatly reduced in Lef1 knockout mice. By examining embryonic mouse tongues in culture we determined that activation of Wnt/β-catenin signaling up-regulates Shh expression. We observed that blocking Shh signaling in cultured tongue explants enhanced papillae formation and was accompanied by an up-regulation of Wnt/β-catenin signaling, indicating that Shh inhibits the Wnt/β-catenin pathway. Exogenously added Shh suppressed expression of endogenous Shh and inhibited Wnt/β-catenin signaling (assessed in TOPGAL mice), further implicating Shh as an inhibitor of the Wnt/β-catenin pathway. Our observations indicate that Wnt/β-catenin signaling and interactions between the Wnt and Shh pathways play essential roles in the development of fungiform papillae.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0607399104</identifier><identifier>PMID: 17284610</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Antibodies ; beta Catenin - metabolism ; Biological Sciences ; Catenins ; Cells ; Complementary DNA ; Gene Expression Regulation ; Gustatory perception ; Hedgehog Proteins - physiology ; In situ hybridization ; Lymphoid Enhancer-Binding Factor 1 - deficiency ; Lymphoid Enhancer-Binding Factor 1 - physiology ; Mandible ; Mice ; Mice, Knockout ; Papillae ; Proteins ; Rodents ; Signal Transduction ; Taste Buds - growth & development ; Tongue ; Transcription factors ; Wnt Proteins - antagonists & inhibitors ; Wnt Proteins - deficiency ; Wnt Proteins - physiology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2007-02, Vol.104 (7), p.2253-2258</ispartof><rights>Copyright 2007 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 13, 2007</rights><rights>2007 by The National Academy of Sciences of the USA 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-43f12656520c09fc5f7e63ea4590ab9078a8c2072f04901da1d72caee783e1083</citedby><cites>FETCH-LOGICAL-c550t-43f12656520c09fc5f7e63ea4590ab9078a8c2072f04901da1d72caee783e1083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/104/7.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25426457$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25426457$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17284610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwatsuki, Ken</creatorcontrib><creatorcontrib>Liu, Hong-Xiang</creatorcontrib><creatorcontrib>Grónder, Albert</creatorcontrib><creatorcontrib>Singer, Meredith A</creatorcontrib><creatorcontrib>Lane, Timothy F</creatorcontrib><creatorcontrib>Grosschedl, Rudolf</creatorcontrib><creatorcontrib>Mistretta, Charlotte M</creatorcontrib><creatorcontrib>Margolskee, Robert F</creatorcontrib><title>Wnt signaling interacts with Shh to regulate taste papilla development</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Wnt and Shh signaling pathways are critical for the development and maturation of many epithelial tissues. Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expression in fungiform papillae and formation of normal mature fungiform papillae depend on signaling through Wnt and β-catenin. We observed that during fungiform papilla formation in mice, Shh and components of the Wnt/β-catenin signaling pathway are expressed together in the developing placode. The elimination of Wnt/β-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression. In addition, the size and number of fungiform papillae were greatly reduced in Lef1 knockout mice. By examining embryonic mouse tongues in culture we determined that activation of Wnt/β-catenin signaling up-regulates Shh expression. We observed that blocking Shh signaling in cultured tongue explants enhanced papillae formation and was accompanied by an up-regulation of Wnt/β-catenin signaling, indicating that Shh inhibits the Wnt/β-catenin pathway. Exogenously added Shh suppressed expression of endogenous Shh and inhibited Wnt/β-catenin signaling (assessed in TOPGAL mice), further implicating Shh as an inhibitor of the Wnt/β-catenin pathway. Our observations indicate that Wnt/β-catenin signaling and interactions between the Wnt and Shh pathways play essential roles in the development of fungiform papillae.</description><subject>Animals</subject><subject>Antibodies</subject><subject>beta Catenin - metabolism</subject><subject>Biological Sciences</subject><subject>Catenins</subject><subject>Cells</subject><subject>Complementary DNA</subject><subject>Gene Expression Regulation</subject><subject>Gustatory perception</subject><subject>Hedgehog Proteins - physiology</subject><subject>In situ hybridization</subject><subject>Lymphoid Enhancer-Binding Factor 1 - deficiency</subject><subject>Lymphoid Enhancer-Binding Factor 1 - physiology</subject><subject>Mandible</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Papillae</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Taste Buds - growth & development</subject><subject>Tongue</subject><subject>Transcription factors</subject><subject>Wnt Proteins - antagonists & inhibitors</subject><subject>Wnt Proteins - deficiency</subject><subject>Wnt Proteins - physiology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1vFDEQxS0EIkegpgJWKaDaZOz1Z4OEIgJIkShCRGk5Pu-eT771YnsD-e_x6U65QAGNbWl-88ZvHkIvMZxiEN3ZNJp8Crw-lcJAH6EFBoVbThU8RgsAIlpJCT1Cz3JeA4BiEp6iIyyIpBzDAl18H0uT_TCa4Meh8WNxydiSm5--rJqr1aopsUlumIMprikm13Mykw_BNEt360KcNm4sz9GT3oTsXuzvY3R98fHb-ef28uunL-cfLlvLGJSWdj0mnHFGwILqLeuF450zlCkwNwqENNISEKSH6gAvDV4KYo1zQnYOg-yO0fud7jTfbNzS1tHJBD0lvzHpTkfj9Z-V0a_0EG81FooSLKrA271Aij9ml4ve-GxdtTO6OGfNFYAEwv8L4rrKTjJcwZO_wHWcU91n1gQw7STFpEJnO8immHNy_f2XMehtknqbpD4kWTteP3R64PfRPQC2nQc5qoUmhHUVePdPQPdzCMX9KpV8tSPXucR0jxJGCadsu7Q3u3pvojZD8llfX1VzHYCgQtRZvwHaDsQD</recordid><startdate>20070213</startdate><enddate>20070213</enddate><creator>Iwatsuki, Ken</creator><creator>Liu, Hong-Xiang</creator><creator>Grónder, Albert</creator><creator>Singer, Meredith A</creator><creator>Lane, Timothy F</creator><creator>Grosschedl, Rudolf</creator><creator>Mistretta, Charlotte M</creator><creator>Margolskee, Robert F</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070213</creationdate><title>Wnt signaling interacts with Shh to regulate taste papilla development</title><author>Iwatsuki, Ken ; 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Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expression in fungiform papillae and formation of normal mature fungiform papillae depend on signaling through Wnt and β-catenin. We observed that during fungiform papilla formation in mice, Shh and components of the Wnt/β-catenin signaling pathway are expressed together in the developing placode. The elimination of Wnt/β-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression. In addition, the size and number of fungiform papillae were greatly reduced in Lef1 knockout mice. By examining embryonic mouse tongues in culture we determined that activation of Wnt/β-catenin signaling up-regulates Shh expression. We observed that blocking Shh signaling in cultured tongue explants enhanced papillae formation and was accompanied by an up-regulation of Wnt/β-catenin signaling, indicating that Shh inhibits the Wnt/β-catenin pathway. Exogenously added Shh suppressed expression of endogenous Shh and inhibited Wnt/β-catenin signaling (assessed in TOPGAL mice), further implicating Shh as an inhibitor of the Wnt/β-catenin pathway. Our observations indicate that Wnt/β-catenin signaling and interactions between the Wnt and Shh pathways play essential roles in the development of fungiform papillae.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>17284610</pmid><doi>10.1073/pnas.0607399104</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies beta Catenin - metabolism Biological Sciences Catenins Cells Complementary DNA Gene Expression Regulation Gustatory perception Hedgehog Proteins - physiology In situ hybridization Lymphoid Enhancer-Binding Factor 1 - deficiency Lymphoid Enhancer-Binding Factor 1 - physiology Mandible Mice Mice, Knockout Papillae Proteins Rodents Signal Transduction Taste Buds - growth & development Tongue Transcription factors Wnt Proteins - antagonists & inhibitors Wnt Proteins - deficiency Wnt Proteins - physiology |
| title | Wnt signaling interacts with Shh to regulate taste papilla development |
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