{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Manual"},"PMID":{"@attributes":{"Version":"1"},"@text":"12730124"},"DateCompleted":{"Year":"2003","Month":"06","Day":"19"},"DateRevised":{"Year":"2021","Month":"11","Day":"09"},"Article":{"@attributes":{"PubModel":"Print-Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Print"},"@text":"0890-9369"},"JournalIssue":{"@attributes":{"CitedMedium":"Print"},"Volume":"17","Issue":"10","PubDate":{"Year":"2003","Month":"May","Day":"15"}},"Title":"Genes & development","ISOAbbreviation":"Genes Dev"},"ArticleTitle":"Notch signaling regulates left-right asymmetry determination by inducing Nodal expression.","Pagination":{"StartPage":"1207","EndPage":"1212","MedlinePgn":"1207-12"},"Abstract":{"AbstractText":["Generation of left-right asymmetry is an integral part of the establishment of the vertebrate body plan. Here we show that the Notch signaling pathway plays a primary role in the establishment of left-right asymmetry in mice by directly regulating expression of the Nodal gene. Embryos mutant for the Notch ligand Dll1 or doubly mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry. Analysis of the enhancer regulating node-specific Nodal expression revealed the presence of binding sites for the RBP-J protein, the primary transcriptional mediator of Notch signaling. Mutation of these sites destroyed the ability of this enhancer to direct node-specific gene expression in transgenic mice. Our results demonstrate that Dll1-mediated Notch signaling is essential for generation of left-right asymmetry, and that the Notch pathway acts upstream of Nodal expression during left-right asymmetry determination in mice."]},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Krebs","ForeName":"Luke T","Initials":"LT","AffiliationInfo":[{"Affiliation":"The Jackson Laboratory, Bar Harbor, Maine 04609, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Iwai","ForeName":"Naomi","Initials":"N"},{"@attributes":{"ValidYN":"Y"},"LastName":"Nonaka","ForeName":"Shigenori","Initials":"S"},{"@attributes":{"ValidYN":"Y"},"LastName":"Welsh","ForeName":"Ian C","Initials":"IC"},{"@attributes":{"ValidYN":"Y"},"LastName":"Lan","ForeName":"Yu","Initials":"Y"},{"@attributes":{"ValidYN":"Y"},"LastName":"Jiang","ForeName":"Rulang","Initials":"R"},{"@attributes":{"ValidYN":"Y"},"LastName":"Saijoh","ForeName":"Yukio","Initials":"Y"},{"@attributes":{"ValidYN":"Y"},"LastName":"O'Brien","ForeName":"Timothy P","Initials":"TP"},{"@attributes":{"ValidYN":"Y"},"LastName":"Hamada","ForeName":"Hiroshi","Initials":"H"},{"@attributes":{"ValidYN":"Y"},"LastName":"Gridley","ForeName":"Thomas","Initials":"T"}]},"Language":["eng"],"GrantList":{"@attributes":{"CompleteYN":"Y"},"Grant":[{"GrantID":"HD36434","Acronym":"HD","Agency":"NICHD NIH HHS","Country":"United States"},{"GrantID":"NS36437","Acronym":"NS","Agency":"NINDS NIH HHS","Country":"United States"},{"GrantID":"P30 CA034196","Acronym":"CA","Agency":"NCI NIH HHS","Country":"United States"},{"GrantID":"HD41066","Acronym":"HD","Agency":"NICHD NIH HHS","Country":"United States"},{"GrantID":"R01 HD041066","Acronym":"HD","Agency":"NICHD NIH HHS","Country":"United States"},{"GrantID":"R01 NS036437","Acronym":"NS","Agency":"NINDS NIH HHS","Country":"United States"},{"GrantID":"CA34196","Acronym":"CA","Agency":"NCI NIH HHS","Country":"United States"}]},"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"},{"@attributes":{"UI":"D013487"},"@text":"Research Support, U.S. Gov't, P.H.S."}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2003","Month":"05","Day":"02"}]},"MedlineJournalInfo":{"Country":"United States","MedlineTA":"Genes Dev","NlmUniqueID":"8711660","ISSNLinking":"0890-9369"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D047908"},"@text":"Intracellular Signaling Peptides and Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D055458"},"@text":"Left-Right Determination Factors"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D008565"},"@text":"Membrane Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D055457"},"@text":"Nodal Protein"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C526008"},"@text":"Nodal protein, mouse"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D051880"},"@text":"Receptors, Notch"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D016212"},"@text":"Transforming Growth Factor beta"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C064045"},"@text":"delta protein"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D000818","MajorTopicYN":"N"},"@text":"Animals"}},{"DescriptorName":{"@attributes":{"UI":"D001665","MajorTopicYN":"N"},"@text":"Binding Sites"}},{"DescriptorName":{"@attributes":{"UI":"D019521","MajorTopicYN":"N"},"@text":"Body Patterning"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"Y"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D002923","MajorTopicYN":"N"},"@text":"Cilia"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D004742","MajorTopicYN":"N"},"@text":"Enhancer Elements, Genetic"}},{"DescriptorName":{"@attributes":{"UI":"D018507","MajorTopicYN":"N"},"@text":"Gene Expression Regulation, Developmental"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"Y"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D047908","MajorTopicYN":"N"},"@text":"Intracellular Signaling Peptides and Proteins"}},{"DescriptorName":{"@attributes":{"UI":"D055458","MajorTopicYN":"N"},"@text":"Left-Right Determination Factors"}},{"DescriptorName":{"@attributes":{"UI":"D008565","MajorTopicYN":"N"},"@text":"Membrane Proteins"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"},{"@attributes":{"UI":"Q000502","MajorTopicYN":"Y"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D051379","MajorTopicYN":"N"},"@text":"Mice"}},{"DescriptorName":{"@attributes":{"UI":"D009154","MajorTopicYN":"N"},"@text":"Mutation"}},{"DescriptorName":{"@attributes":{"UI":"D055457","MajorTopicYN":"N"},"@text":"Nodal Protein"}},{"DescriptorName":{"@attributes":{"UI":"D051880","MajorTopicYN":"N"},"@text":"Receptors, Notch"}},{"DescriptorName":{"@attributes":{"UI":"D015398","MajorTopicYN":"N"},"@text":"Signal Transduction"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"N"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D016212","MajorTopicYN":"N"},"@text":"Transforming Growth Factor beta"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]}]}},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"pubmed"},"Year":"2003","Month":"5","Day":"6","Hour":"5","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2003","Month":"6","Day":"20","Hour":"5","Minute":"0"},{"@attributes":{"PubStatus":"entrez"},"Year":"2003","Month":"5","Day":"6","Hour":"5","Minute":"0"},{"@attributes":{"PubStatus":"pmc-release"},"Year":"2003","Month":"11","Day":"15"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"12730124"},{"@attributes":{"IdType":"pmc"},"@text":"PMC196059"},{"@attributes":{"IdType":"doi"},"@text":"10.1101\/gad.1084703"},{"@attributes":{"IdType":"pii"},"@text":"U-10847Rsp"}]},"ReferenceList":[{"Reference":[{"Citation":"Adachi H, Saijoh Y, Mochida K, Ohishi S, Hashiguchi H, Hirao A, 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