Na,K-ATPase is essential for embryonic heart development in the zebrafish
Na,K-ATPase is an essential gene maintaining electrochemical gradients across the plasma membrane. Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,KATPase during embryonic heart d...
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| Veröffentlicht in: | Development (Cambridge) 2003-12, Vol.130 (25), p.6165-6173 |
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| creator | Shu, Xiaodong Cheng, Karen Patel, Neil Chen, Fuhua Joseph, Elaine Tsai, Huai-Jen Chen, Jau-Nian |
| description | Na,K-ATPase is an essential gene maintaining electrochemical gradients across the plasma membrane. Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,KATPase during embryonic heart development. Here, we report the identification of a zebrafish mutant, heart and mind , which exhibits multiple cardiac defects, including the primitive heart tube extension abnormality, aberrant cardiomyocyte differentiation, and reduced heart rate and contractility. Molecular cloning reveals that the heart and mind lesion resides in the α1B1 isoform of Na,K-ATPase. Blocking Na,K-ATPase α1B1 activity by pharmacological means or by morpholino antisense oligonucleotides phenocopies the patterning and functional defects of heart and mind mutant hearts, suggesting crucial roles for Na,KATPase α1B1 in embryonic zebrafish hearts. In addition to α1B1, the Na,K-ATPase α2 isoform is required for embryonic cardiac patterning. Although the α1B1 andα 2 isoforms share high degrees of similarities in their coding sequences, they have distinct roles in patterning zebrafish hearts. The phenotypes of heart and mind mutants can be rescued by supplementingα 1B1 , but not α 2 , mRNA to the mutant embryos, demonstrating that α1B1 and α2 are not functionally equivalent. Furthermore, instead of interfering with primitive heart tube formation or cardiac chamber differentiation, blocking the translation of Na,KATPaseα 2 isoform leads to cardiac laterality defects. |
| doi_str_mv | 10.1242/dev.00844 |
| format | Article |
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Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,KATPase during embryonic heart development. Here, we report the identification of a zebrafish mutant, heart and mind , which exhibits multiple cardiac defects, including the primitive heart tube extension abnormality, aberrant cardiomyocyte differentiation, and reduced heart rate and contractility. Molecular cloning reveals that the heart and mind lesion resides in the α1B1 isoform of Na,K-ATPase. Blocking Na,K-ATPase α1B1 activity by pharmacological means or by morpholino antisense oligonucleotides phenocopies the patterning and functional defects of heart and mind mutant hearts, suggesting crucial roles for Na,KATPase α1B1 in embryonic zebrafish hearts. In addition to α1B1, the Na,K-ATPase α2 isoform is required for embryonic cardiac patterning. Although the α1B1 andα 2 isoforms share high degrees of similarities in their coding sequences, they have distinct roles in patterning zebrafish hearts. The phenotypes of heart and mind mutants can be rescued by supplementingα 1B1 , but not α 2 , mRNA to the mutant embryos, demonstrating that α1B1 and α2 are not functionally equivalent. Furthermore, instead of interfering with primitive heart tube formation or cardiac chamber differentiation, blocking the translation of Na,KATPaseα 2 isoform leads to cardiac laterality defects.</description><identifier>ISSN: 0950-1991</identifier><identifier>EISSN: 1477-9129</identifier><identifier>DOI: 10.1242/dev.00844</identifier><identifier>PMID: 14602677</identifier><language>eng</language><publisher>England: The Company of Biologists Limited</publisher><subject>Animals ; Base Sequence ; Danio rerio ; DNA Primers ; Embryo, Nonmammalian - physiology ; Gene Expression Regulation, Developmental ; Genes, Essential ; Heart - embryology ; Heart Defects, Congenital - enzymology ; Heart Defects, Congenital - genetics ; In Situ Hybridization ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Molecular Sequence Data ; Morphogenesis - physiology ; Mutation ; Polymerase Chain Reaction ; Sodium-Potassium-Exchanging ATPase - genetics ; Sodium-Potassium-Exchanging ATPase - metabolism ; Zebrafish - embryology ; Zebrafish Proteins - genetics</subject><ispartof>Development (Cambridge), 2003-12, Vol.130 (25), p.6165-6173</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-7b0e4ae8b7c5641c4f116e27de62a9bb041856778dc70b62d9c846f9e55307853</citedby><cites>FETCH-LOGICAL-c452t-7b0e4ae8b7c5641c4f116e27de62a9bb041856778dc70b62d9c846f9e55307853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3665,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14602677$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shu, Xiaodong</creatorcontrib><creatorcontrib>Cheng, Karen</creatorcontrib><creatorcontrib>Patel, Neil</creatorcontrib><creatorcontrib>Chen, Fuhua</creatorcontrib><creatorcontrib>Joseph, Elaine</creatorcontrib><creatorcontrib>Tsai, Huai-Jen</creatorcontrib><creatorcontrib>Chen, Jau-Nian</creatorcontrib><title>Na,K-ATPase is essential for embryonic heart development in the zebrafish</title><title>Development (Cambridge)</title><addtitle>Development</addtitle><description>Na,K-ATPase is an essential gene maintaining electrochemical gradients across the plasma membrane. Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,KATPase during embryonic heart development. Here, we report the identification of a zebrafish mutant, heart and mind , which exhibits multiple cardiac defects, including the primitive heart tube extension abnormality, aberrant cardiomyocyte differentiation, and reduced heart rate and contractility. Molecular cloning reveals that the heart and mind lesion resides in the α1B1 isoform of Na,K-ATPase. Blocking Na,K-ATPase α1B1 activity by pharmacological means or by morpholino antisense oligonucleotides phenocopies the patterning and functional defects of heart and mind mutant hearts, suggesting crucial roles for Na,KATPase α1B1 in embryonic zebrafish hearts. In addition to α1B1, the Na,K-ATPase α2 isoform is required for embryonic cardiac patterning. Although the α1B1 andα 2 isoforms share high degrees of similarities in their coding sequences, they have distinct roles in patterning zebrafish hearts. The phenotypes of heart and mind mutants can be rescued by supplementingα 1B1 , but not α 2 , mRNA to the mutant embryos, demonstrating that α1B1 and α2 are not functionally equivalent. Furthermore, instead of interfering with primitive heart tube formation or cardiac chamber differentiation, blocking the translation of Na,KATPaseα 2 isoform leads to cardiac laterality defects.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Danio rerio</subject><subject>DNA Primers</subject><subject>Embryo, Nonmammalian - physiology</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genes, Essential</subject><subject>Heart - embryology</subject><subject>Heart Defects, Congenital - enzymology</subject><subject>Heart Defects, Congenital - genetics</subject><subject>In Situ Hybridization</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Morphogenesis - physiology</subject><subject>Mutation</subject><subject>Polymerase Chain Reaction</subject><subject>Sodium-Potassium-Exchanging ATPase - genetics</subject><subject>Sodium-Potassium-Exchanging ATPase - metabolism</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish Proteins - genetics</subject><issn>0950-1991</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0LtOwzAUBmALgWgpDLwA8oSERIrt-BKPVcWlogKGMlt2ctIYJU2xU1B5egKtxMh0zvDpXH6EzikZU8bZTQEfY0Iyzg_QkHKlEk2ZPkRDogVJqNZ0gE5ifCOEpFKpYzSgXBLWt0M0e7LXj8lk8WIjYB8xxAirztsal23A0LiwbVc-xxXY0OF-EdTtuukJ9ivcVYC_wAVb-lidoqPS1hHO9nWEXu9uF9OHZP58P5tO5knOBesS5QhwC5lTuZCc5rykVAJTBUhmtXOE00z0p2VFroiTrNB5xmWpQYiUqEykI3S5m7sO7fsGYmcaH3Ooa7uCdhONomnGU0b-hVQzlnEte3i1g3loYwxQmnXwjQ1bQ4n5Cdj0f5vfgHt7sR-6cQ0Uf3KfaA_GO1D5ZfXpAxjn27pd-thFs8_P0JQYJoykUqTf5rGE6A</recordid><startdate>20031222</startdate><enddate>20031222</enddate><creator>Shu, Xiaodong</creator><creator>Cheng, Karen</creator><creator>Patel, Neil</creator><creator>Chen, Fuhua</creator><creator>Joseph, Elaine</creator><creator>Tsai, Huai-Jen</creator><creator>Chen, Jau-Nian</creator><general>The Company of Biologists Limited</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20031222</creationdate><title>Na,K-ATPase is essential for embryonic heart development in the zebrafish</title><author>Shu, Xiaodong ; Cheng, Karen ; Patel, Neil ; Chen, Fuhua ; Joseph, Elaine ; Tsai, Huai-Jen ; Chen, Jau-Nian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-7b0e4ae8b7c5641c4f116e27de62a9bb041856778dc70b62d9c846f9e55307853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Danio rerio</topic><topic>DNA Primers</topic><topic>Embryo, Nonmammalian - physiology</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genes, Essential</topic><topic>Heart - embryology</topic><topic>Heart Defects, Congenital - enzymology</topic><topic>Heart Defects, Congenital - genetics</topic><topic>In Situ Hybridization</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Morphogenesis - physiology</topic><topic>Mutation</topic><topic>Polymerase Chain Reaction</topic><topic>Sodium-Potassium-Exchanging ATPase - genetics</topic><topic>Sodium-Potassium-Exchanging ATPase - metabolism</topic><topic>Zebrafish - embryology</topic><topic>Zebrafish Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shu, Xiaodong</creatorcontrib><creatorcontrib>Cheng, Karen</creatorcontrib><creatorcontrib>Patel, Neil</creatorcontrib><creatorcontrib>Chen, Fuhua</creatorcontrib><creatorcontrib>Joseph, Elaine</creatorcontrib><creatorcontrib>Tsai, Huai-Jen</creatorcontrib><creatorcontrib>Chen, Jau-Nian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Development (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shu, Xiaodong</au><au>Cheng, Karen</au><au>Patel, Neil</au><au>Chen, Fuhua</au><au>Joseph, Elaine</au><au>Tsai, Huai-Jen</au><au>Chen, Jau-Nian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Na,K-ATPase is essential for embryonic heart development in the zebrafish</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2003-12-22</date><risdate>2003</risdate><volume>130</volume><issue>25</issue><spage>6165</spage><epage>6173</epage><pages>6165-6173</pages><issn>0950-1991</issn><eissn>1477-9129</eissn><abstract>Na,K-ATPase is an essential gene maintaining electrochemical gradients across the plasma membrane. Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,KATPase during embryonic heart development. Here, we report the identification of a zebrafish mutant, heart and mind , which exhibits multiple cardiac defects, including the primitive heart tube extension abnormality, aberrant cardiomyocyte differentiation, and reduced heart rate and contractility. Molecular cloning reveals that the heart and mind lesion resides in the α1B1 isoform of Na,K-ATPase. Blocking Na,K-ATPase α1B1 activity by pharmacological means or by morpholino antisense oligonucleotides phenocopies the patterning and functional defects of heart and mind mutant hearts, suggesting crucial roles for Na,KATPase α1B1 in embryonic zebrafish hearts. In addition to α1B1, the Na,K-ATPase α2 isoform is required for embryonic cardiac patterning. Although the α1B1 andα 2 isoforms share high degrees of similarities in their coding sequences, they have distinct roles in patterning zebrafish hearts. The phenotypes of heart and mind mutants can be rescued by supplementingα 1B1 , but not α 2 , mRNA to the mutant embryos, demonstrating that α1B1 and α2 are not functionally equivalent. Furthermore, instead of interfering with primitive heart tube formation or cardiac chamber differentiation, blocking the translation of Na,KATPaseα 2 isoform leads to cardiac laterality defects.</abstract><cop>England</cop><pub>The Company of Biologists Limited</pub><pmid>14602677</pmid><doi>10.1242/dev.00844</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Animals Base Sequence Danio rerio DNA Primers Embryo, Nonmammalian - physiology Gene Expression Regulation, Developmental Genes, Essential Heart - embryology Heart Defects, Congenital - enzymology Heart Defects, Congenital - genetics In Situ Hybridization Isoenzymes - genetics Isoenzymes - metabolism Molecular Sequence Data Morphogenesis - physiology Mutation Polymerase Chain Reaction Sodium-Potassium-Exchanging ATPase - genetics Sodium-Potassium-Exchanging ATPase - metabolism Zebrafish - embryology Zebrafish Proteins - genetics |
| title | Na,K-ATPase is essential for embryonic heart development in the zebrafish |
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