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<PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Manual"><PMID Version="1">11703930</PMID><DateCompleted><Year>2001</Year><Month>12</Month><Day>05</Day></DateCompleted><DateRevised><Year>2026</Year><Month>01</Month><Day>28</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1534-5807</ISSN><JournalIssue CitedMedium="Print"><Volume>1</Volume><Issue>1</Issue><PubDate><Year>2001</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Developmental cell</Title><ISOAbbreviation>Dev Cell</ISOAbbreviation></Journal><ArticleTitle>Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2.</ArticleTitle><Pagination><StartPage>127</StartPage><EndPage>138</EndPage><MedlinePgn>127-38</MedlinePgn></Pagination><Abstract><AbstractText>The role of Lefty2 in left-right patterning was investigated by analysis of mutant mice that lack asymmetric expression of lefty2. These animals exhibited various situs defects including left isomerism. The asymmetric expression of nodal was prolonged and the expression of Pitx2 was upregulated in the mutant embryos. The absence of Lefty2 conferred on Nodal the ability to diffuse over a long distance. Thus, Nodal-responsive genes, including Pitx2, that are normally expressed on the left side were expressed bilaterally in the mutant embryos, even though nodal expression was confined to the left side. These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Meno</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Takeuchi</LastName><ForeName>J</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Sakuma</LastName><ForeName>R</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Koshiba-Takeuchi</LastName><ForeName>K</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Ohishi</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Saijoh</LastName><ForeName>Y</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Miyazaki</LastName><ForeName>J</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>ten Dijke</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Ogura</LastName><ForeName>T</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Hamada</LastName><ForeName>H</ForeName><Initials>H</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Dev Cell</MedlineTA><NlmUniqueID>101120028</NlmUniqueID><ISSNLinking>1534-5807</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004268">DNA-Binding Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018398">Homeodomain Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D055458">Left-Right Determination Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D055457">Nodal Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009687">Nuclear Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051899">Smad2 Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015534">Trans-Activators</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014157">Transcription Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016212">Transforming Growth Factor beta</NameOfSubstance></Chemical><Chemical><RegistryNumber>184787-43-7</RegistryNumber><NameOfSubstance UI="D000097577">Homeobox Protein PITX2</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C526008">Nodal protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497783">Smad2 protein, mouse</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019521" MajorTopicYN="N">Body Patterning</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004268" MajorTopicYN="N">DNA-Binding Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004058" MajorTopicYN="N">Diffusion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D025461" MajorTopicYN="N">Feedback, Physiological</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017353" MajorTopicYN="N">Gene Deletion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018507" MajorTopicYN="N">Gene Expression Regulation, Developmental</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018398" MajorTopicYN="N">Homeodomain Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055458" MajorTopicYN="N">Left-Right Determination Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055457" MajorTopicYN="N">Nodal Protein</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009687" MajorTopicYN="Y">Nuclear Proteins</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051899" MajorTopicYN="N">Smad2 Protein</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015534" MajorTopicYN="N">Trans-Activators</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014157" MajorTopicYN="N">Transcription Factors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016212" MajorTopicYN="N">Transforming Growth Factor beta</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000097577" MajorTopicYN="N">Homeobox Protein PITX2</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>11</Month><Day>13</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2002</Year><Month>1</Month><Day>5</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>11</Month><Day>13</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11703930</ArticleId><ArticleId IdType="doi">10.1016/s1534-5807(01)00006-5</ArticleId><ArticleId IdType="pii">S1534-5807(01)00006-5</ArticleId></ArticleIdList></PubmedData></PubmedArticle></PubmedArticleSet>