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Reversal of left-right asymmetry induced by aberrant nodal signaling in the node of mouse embryos

2009-12Journal article Open access
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dc.contributor.authorOki, Shinya
dc.contributor.authorKitajima, Keiko
dc.contributor.authorMarques, Sara
dc.contributor.authorBelo, José A.
dc.contributor.authorYokoyama, Takahiko
dc.contributor.authorHamada, Hiroshi
dc.contributor.authorMeno, Chikara
dc.date.accessioned2018-12-07T14:52:53Z
dc.date.available2018-12-07T14:52:53Z
dc.date.issued2009-12
dc.description.abstractThe node at the anterior tip of the primitive streak serves as an initial generator of the left-right (L-R) axis in mammalian embryos. We now show that a small disturbance in molecular signaling at the node is responsible for the L-R reversal of visceral organs in the inv mutant mouse. In the node of wild-type embryos, the expression of Nodal and Cerl2 (Dand5), which encodes an inhibitor of Nodal, is asymmetric, with the level of Nodal expression being higher on the left side and that of Cerl2 expression higher on the right. In inv/inv embryos, however, a localized reduction in the level of Cerl2 expression results in upregulation of the Nodal signal and a consequent induction of Lefty expression in the node. The ectopic expression of Lefty1 delays the onset of Nodal expression in the lateral plate mesoderm. L-R asymmetry of Cerl2 expression in the node also becomes reversed in a manner dependent on the Nodal signal. Nodal expression in the lateral plate mesoderm then appears on the right side, probably reflecting the balance between Nodal and Cerl2 in the node. The inhibition of Cerl2 expression by the Nodal signal suggests a mechanism for amplification of the cue for L-R asymmetry provided by nodal flow and for stabilization of asymmetric gene expression around the node. In inv/inv embryos, this system may function in reverse as a result of ectopic production of Lefty, which inhibits the Nodal signal on the left side in a manner dependent on leftward nodal flow.
dc.description.sponsorshipMinistry of Education, Culture, Sports, Science, and Technology of Japan; CREST; Kyushu University; Naito Foundation
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1242/dev.039305
dc.identifier.issn0950-1991
dc.identifier.urihttp://hdl.handle.net/10400.1/11252
dc.language.isoeng
dc.peerreviewedyes
dc.publisherCompany of Biologists
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectLeft-right axis
dc.subjectSitus-inversus
dc.subjectLateral plate
dc.subjectPrimary cilia
dc.subjectExpression
dc.subjectGene
dc.subjectPitx2
dc.subjectPathway
dc.subjectInv
dc.subjectRequires
dc.subjectNode
dc.subjectMouse
dc.subjectNodal signal
dc.titleReversal of left-right asymmetry induced by aberrant nodal signaling in the node of mouse embryos
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage3925
oaire.citation.issue23
oaire.citation.startPage3917
oaire.citation.titleDevelopment
oaire.citation.volume136
person.familyNameOki
person.familyNameMarques
person.familyNameBelo
person.givenNameShinya
person.givenNameSara
person.givenNameJosé A.
person.identifier1000090452713
person.identifier.ciencia-idBB17-0F5D-A4FB
person.identifier.ciencia-idBF13-08E9-25E6
person.identifier.orcid0000-0002-4767-3259
person.identifier.orcid0000-0001-6784-5612
person.identifier.orcid0000-0001-7384-0949
person.identifier.ridF-4444-2012
person.identifier.scopus-author-id23019582100
person.identifier.scopus-author-id6602141392
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication0e47f69c-9f93-46f3-8523-31b761cc80bb
relation.isAuthorOfPublication20dd7142-5b7a-465f-8943-a6ac33b91df1
relation.isAuthorOfPublication4bebeb48-6fac-41a9-8363-f849def5e019
relation.isAuthorOfPublication.latestForDiscovery0e47f69c-9f93-46f3-8523-31b761cc80bb

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