Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer
Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix-loop-helix transcription factor dHAND is also required for craniofacial...
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| Veröffentlicht in: | Genes & development 2001-11, Vol.15 (22), p.3039-3049 |
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| creator | Charité, J McFadden, D G Merlo, G Levi, G Clouthier, D E Yanagisawa, M Richardson, J A Olson, E N |
| description | Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix-loop-helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. |
| doi_str_mv | 10.1101/gad.931701 |
| format | Article |
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The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix-loop-helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.931701</identifier><identifier>PMID: 11711438</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Animals ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors ; Binding Sites ; Chick Embryo ; COS Cells ; dHAND gene ; Dlx6 protein ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - metabolism ; Down-Regulation ; EdnrA gene ; Endothelin receptor A ; Endothelin-1 - metabolism ; ET-1 gene ; Gene Deletion ; Gene Expression Regulation ; Genes, Reporter ; Homeodomain Proteins - metabolism ; Homeodomain Proteins - physiology ; In Situ Hybridization ; Mice ; Mice, Transgenic ; Models, Genetic ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Tertiary ; Research Paper ; Signal Transduction ; Transcription Factors - chemistry ; Transcription Factors - metabolism ; Transcription, Genetic ; Zebrafish Proteins</subject><ispartof>Genes & development, 2001-11, Vol.15 (22), p.3039-3049</ispartof><rights>Copyright © 2001, Cold Spring Harbor Laboratory Press 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-d4ae33759f4e3118424425987f28c7f6e83d7fa5decc41a741789f68c973eed83</citedby><cites>FETCH-LOGICAL-c402t-d4ae33759f4e3118424425987f28c7f6e83d7fa5decc41a741789f68c973eed83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC312822/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC312822/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11711438$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Charité, J</creatorcontrib><creatorcontrib>McFadden, D G</creatorcontrib><creatorcontrib>Merlo, G</creatorcontrib><creatorcontrib>Levi, G</creatorcontrib><creatorcontrib>Clouthier, D E</creatorcontrib><creatorcontrib>Yanagisawa, M</creatorcontrib><creatorcontrib>Richardson, J A</creatorcontrib><creatorcontrib>Olson, E N</creatorcontrib><title>Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix-loop-helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Basic Helix-Loop-Helix Transcription Factors</subject><subject>Binding Sites</subject><subject>Chick Embryo</subject><subject>COS Cells</subject><subject>dHAND gene</subject><subject>Dlx6 protein</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation</subject><subject>EdnrA gene</subject><subject>Endothelin receptor A</subject><subject>Endothelin-1 - metabolism</subject><subject>ET-1 gene</subject><subject>Gene Deletion</subject><subject>Gene Expression Regulation</subject><subject>Genes, Reporter</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Homeodomain Proteins - physiology</subject><subject>In Situ Hybridization</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Models, Genetic</subject><subject>Molecular Sequence Data</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>Research Paper</subject><subject>Signal Transduction</subject><subject>Transcription Factors - chemistry</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Zebrafish Proteins</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkcFOGzEQhi0EgpD2wgNUe-JQscFje9f2gQMiUCpFIFXQq2Xs2exWjh28m6q8PYsSUTiNZuabmV_zE3ICdAZA4Xxp_UxzkBT2yAQqoctKSLlPJlRpWmpe6yNy3Pd_KKU1retDcgQgAQRXE_L7VwpYpKaYh3910cUi43IT7NCl-Fa1scDo09Bi6GIJpcf1mGMczgp_e3k3L56yja7tbChsdu0It2OO-Qs5aGzo8esuTsnjzfXD1W25uP_x8-pyUTpB2VB6YZFzWelGIAdQggnBKq1kw5STTY2Ke9nYyqNzAqwUIJVuauW05Ihe8Sm52O5db55W6N2oLNtg1rlb2fxiku3M507sWrNMfw0Hphgb50938zk9b7AfzKrrHYZgI6ZNb0AxwagSI_h9C7qc-j5j834DqHlzwYwumK0LI_zto6r_6O7t_BU4yIKg</recordid><startdate>20011115</startdate><enddate>20011115</enddate><creator>Charité, J</creator><creator>McFadden, D G</creator><creator>Merlo, G</creator><creator>Levi, G</creator><creator>Clouthier, D E</creator><creator>Yanagisawa, M</creator><creator>Richardson, J A</creator><creator>Olson, E N</creator><general>Cold Spring Harbor Laboratory Press</general><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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20011115</creationdate><title>Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer</title><author>Charité, J ; McFadden, D G ; Merlo, G ; Levi, G ; Clouthier, D E ; Yanagisawa, M ; Richardson, J A ; Olson, E N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-d4ae33759f4e3118424425987f28c7f6e83d7fa5decc41a741789f68c973eed83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Basic Helix-Loop-Helix Transcription Factors</topic><topic>Binding Sites</topic><topic>Chick Embryo</topic><topic>COS Cells</topic><topic>dHAND gene</topic><topic>Dlx6 protein</topic><topic>DNA-Binding Proteins - chemistry</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation</topic><topic>EdnrA gene</topic><topic>Endothelin receptor A</topic><topic>Endothelin-1 - metabolism</topic><topic>ET-1 gene</topic><topic>Gene Deletion</topic><topic>Gene Expression Regulation</topic><topic>Genes, Reporter</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Homeodomain Proteins - physiology</topic><topic>In Situ Hybridization</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Models, Genetic</topic><topic>Molecular Sequence Data</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>Research Paper</topic><topic>Signal Transduction</topic><topic>Transcription Factors - chemistry</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Zebrafish Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Charité, J</creatorcontrib><creatorcontrib>McFadden, D G</creatorcontrib><creatorcontrib>Merlo, G</creatorcontrib><creatorcontrib>Levi, G</creatorcontrib><creatorcontrib>Clouthier, D E</creatorcontrib><creatorcontrib>Yanagisawa, M</creatorcontrib><creatorcontrib>Richardson, J A</creatorcontrib><creatorcontrib>Olson, E N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Charité, J</au><au>McFadden, D G</au><au>Merlo, G</au><au>Levi, G</au><au>Clouthier, D E</au><au>Yanagisawa, M</au><au>Richardson, J A</au><au>Olson, E N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2001-11-15</date><risdate>2001</risdate><volume>15</volume><issue>22</issue><spage>3039</spage><epage>3049</epage><pages>3039-3049</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix-loop-helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>11711438</pmid><doi>10.1101/gad.931701</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Base Sequence Basic Helix-Loop-Helix Transcription Factors Binding Sites Chick Embryo COS Cells dHAND gene Dlx6 protein DNA-Binding Proteins - chemistry DNA-Binding Proteins - metabolism Down-Regulation EdnrA gene Endothelin receptor A Endothelin-1 - metabolism ET-1 gene Gene Deletion Gene Expression Regulation Genes, Reporter Homeodomain Proteins - metabolism Homeodomain Proteins - physiology In Situ Hybridization Mice Mice, Transgenic Models, Genetic Molecular Sequence Data Protein Binding Protein Structure, Tertiary Research Paper Signal Transduction Transcription Factors - chemistry Transcription Factors - metabolism Transcription, Genetic Zebrafish Proteins |
| title | Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer |
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