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Article: Retinoic acid induces down-regulation of Wnt-3a, apoptosis and diversion of tail bud cells to a neural fate in the mouse embryo

TitleRetinoic acid induces down-regulation of Wnt-3a, apoptosis and diversion of tail bud cells to a neural fate in the mouse embryo
Authors
KeywordsApoptosis
Mouse embryo
Neural tissue
Retinoic acid
Tail bud
Wnt-3a
Issue Date1999
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/modo
Citation
Mechanisms Of Development, 1999, v. 84 n. 1-2, p. 17-30 How to Cite?
AbstractThe tail bud comprises the caudal extremity of the vertebrate embryo, containing a pool of pluripotent mesenchymal stem cells that gives rise to almost all the tissues of the sacro-caudal region. Treatment of pregnant mice with 100 mg/kg all-trans retinoic acid at 9.5 days post coitum induces severe truncation of the body axis, providing a model system for studying the mechanisms underlying development of caudal agenesis. In the present study, we find that retinoic acid treatment causes extensive apoptosis of tail bud cells 24 h after treatment. Once the apoptotic cells have been removed, the remaining mesenchymal cells differentiate into an extensive network of ectopic tubules, radially arranged around the notochord. These tubules express Pax-3 and Pax-6 in a regionally-restricted pattern that closely resembles expression in the definitive neural tube. Neurofilament-positive neurons subsequently grow out from the ectopic tubules. Thus, the tail bud cells remaining after retinoic acid-induced apoptosis appear to adopt a neural fate. Wnt-3a, a gene that has been shown to be essential for tail bud formation, is specifically down-regulated in the tail bud of retinoic acid- treated embryos, as early as 2h after retinoic acid treatment and Wnt-3a transcripts become undetectable by 10h. In contrast, Wnt-5a and RAR-γ, are still detectable in the tail bud at that time. Extensive cell death also occurs in the tail bud of embryos homozygous for the vestigial tail mutation, in which there is a marked reduction in Wnt-3a expression. These embryos go on to develop multiple neural tubes in their truncated caudal region. These results suggest that retinoic acid induces downregulation of Wnt-3a which may play an important role in the pathogenesis of axial truncation, involving induction of widespread apoptosis, followed by an alteration of tail bud cell fate to form multiple ectopic neural tubes.
Persistent Identifierhttp://hdl.handle.net/10722/179761
ISSN
2022 Impact Factor: 2.6
2020 SCImago Journal Rankings: 0.890
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorShum, ASWen_US
dc.contributor.authorPoon, LLMen_US
dc.contributor.authorTang, WWTen_US
dc.contributor.authorKoide, Ten_US
dc.contributor.authorChan, BWHen_US
dc.contributor.authorLeung, YCGen_US
dc.contributor.authorShiroishi, Ten_US
dc.contributor.authorCopp, AJen_US
dc.date.accessioned2012-12-19T10:04:23Z-
dc.date.available2012-12-19T10:04:23Z-
dc.date.issued1999en_US
dc.identifier.citationMechanisms Of Development, 1999, v. 84 n. 1-2, p. 17-30en_US
dc.identifier.issn0925-4773en_US
dc.identifier.urihttp://hdl.handle.net/10722/179761-
dc.description.abstractThe tail bud comprises the caudal extremity of the vertebrate embryo, containing a pool of pluripotent mesenchymal stem cells that gives rise to almost all the tissues of the sacro-caudal region. Treatment of pregnant mice with 100 mg/kg all-trans retinoic acid at 9.5 days post coitum induces severe truncation of the body axis, providing a model system for studying the mechanisms underlying development of caudal agenesis. In the present study, we find that retinoic acid treatment causes extensive apoptosis of tail bud cells 24 h after treatment. Once the apoptotic cells have been removed, the remaining mesenchymal cells differentiate into an extensive network of ectopic tubules, radially arranged around the notochord. These tubules express Pax-3 and Pax-6 in a regionally-restricted pattern that closely resembles expression in the definitive neural tube. Neurofilament-positive neurons subsequently grow out from the ectopic tubules. Thus, the tail bud cells remaining after retinoic acid-induced apoptosis appear to adopt a neural fate. Wnt-3a, a gene that has been shown to be essential for tail bud formation, is specifically down-regulated in the tail bud of retinoic acid- treated embryos, as early as 2h after retinoic acid treatment and Wnt-3a transcripts become undetectable by 10h. In contrast, Wnt-5a and RAR-γ, are still detectable in the tail bud at that time. Extensive cell death also occurs in the tail bud of embryos homozygous for the vestigial tail mutation, in which there is a marked reduction in Wnt-3a expression. These embryos go on to develop multiple neural tubes in their truncated caudal region. These results suggest that retinoic acid induces downregulation of Wnt-3a which may play an important role in the pathogenesis of axial truncation, involving induction of widespread apoptosis, followed by an alteration of tail bud cell fate to form multiple ectopic neural tubes.en_US
dc.languageengen_US
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/modoen_US
dc.relation.ispartofMechanisms of Developmenten_US
dc.subjectApoptosis-
dc.subjectMouse embryo-
dc.subjectNeural tissue-
dc.subjectRetinoic acid-
dc.subjectTail bud-
dc.subjectWnt-3a-
dc.subject.meshAnimalsen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCell Death - Drug Effectsen_US
dc.subject.meshCell Differentiationen_US
dc.subject.meshDna-Binding Proteins - Genetics - Metabolismen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshEmbryo, Mammalian - Drug Effectsen_US
dc.subject.meshEye Proteinsen_US
dc.subject.meshFemaleen_US
dc.subject.meshHomeodomain Proteinsen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshMaleen_US
dc.subject.meshMesoderm - Drug Effects - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Icren_US
dc.subject.meshMutationen_US
dc.subject.meshNervous System - Drug Effects - Embryology - Metabolismen_US
dc.subject.meshNervous System Malformations - Chemically Induced - Embryologyen_US
dc.subject.meshNeuronsen_US
dc.subject.meshPaired Box Transcription Factorsen_US
dc.subject.meshPregnancyen_US
dc.subject.meshProteins - Drug Effects - Metabolismen_US
dc.subject.meshRepressor Proteinsen_US
dc.subject.meshTail - Cytology - Drug Effects - Embryologyen_US
dc.subject.meshTranscription Factorsen_US
dc.subject.meshTretinoin - Metabolism - Pharmacologyen_US
dc.subject.meshWnt Proteinsen_US
dc.subject.meshWnt3 Proteinen_US
dc.subject.meshWnt3a Proteinen_US
dc.titleRetinoic acid induces down-regulation of Wnt-3a, apoptosis and diversion of tail bud cells to a neural fate in the mouse embryoen_US
dc.typeArticleen_US
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_US
dc.identifier.authorityPoon, LLM=rp00484en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0925-4773(99)00059-3en_US
dc.identifier.pmid10473117-
dc.identifier.scopuseid_2-s2.0-0032780716en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032780716&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume84en_US
dc.identifier.issue1-2en_US
dc.identifier.spage17en_US
dc.identifier.epage30en_US
dc.identifier.isiWOS:000081559900002-
dc.publisher.placeIrelanden_US
dc.identifier.scopusauthoridShum, ASW=7006909659en_US
dc.identifier.scopusauthoridPoon, LLM=7005441747en_US
dc.identifier.scopusauthoridTang, WWT=36790135700en_US
dc.identifier.scopusauthoridKoide, T=7203046988en_US
dc.identifier.scopusauthoridChan, BWH=17340188900en_US
dc.identifier.scopusauthoridLeung, YCG=54970606000en_US
dc.identifier.scopusauthoridShiroishi, T=7006576277en_US
dc.identifier.scopusauthoridCopp, AJ=7006634311en_US
dc.identifier.issnl0925-4773-

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