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Article: Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity

TitleRetinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity
Authors
Issue Date1992
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 1992, v. 360 n. 6406, p. 737-741 How to Cite?
AbstractIt has been suggested that Hox genes play an important part in the patterning of limbs, vertebrae and craniofacial structures by providing an ordered molecular system of positional values, termed the Hox code. Little is known about the nature of the signals that govern the establishment and regulation of Hox genes, but retinoic acid can affect the expression of these genes in cell lines and in embryonic tissues. On the basis of experimental and clinical evidence, the hindbrain and branchial region of the head are particularly sensitive to the effects of retinoic acid, but the phenotypes are complex and hard to interpret, and how and if they relate to Hox expression has not been clear. Here we follow the changes induced by retinoic acid to hindbrain segmentation and the branchial arches using transgenic mice which contain lacZ reporter genes that reveal the endogenous segment restricted expression of the Hox-B1 (Hox-2.9), Hox-B2 (Hox-2.8) and Krox-20 genes. Our results show that these genes rapidly respond to exposure to retinoic acid at preheadfold stages and undergo a progressive series of changes in segmental expression that are associated with specific phenotypes in hindbrain of first branchial arch. Together the molecular and anatomical alterations indicate that retinoic acid has induced changes in the hindbrain Hox code which result in the homeotic transformation of rhombomeres (r) 2/3 to an r4/5 identity. A main feature of this rhombomeric phenotype is that the trigeminal motor nerve is transformed to a facial identity. Furthermore, in support of this change in rhombomeric identity, neural crest cells derived from r2/3 also express posterior Hox markers suggesting that the retinoic acid-induced transformation extends to multiple components of the first branchial arch.
Persistent Identifierhttp://hdl.handle.net/10722/147373
ISSN
2015 Impact Factor: 38.138
2015 SCImago Journal Rankings: 21.936
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMarshall, Hen_US
dc.contributor.authorNonchev, Sen_US
dc.contributor.authorSham, MHen_US
dc.contributor.authorMuchamore, Ien_US
dc.contributor.authorLumsden, Aen_US
dc.contributor.authorKrumlauf, Ren_US
dc.date.accessioned2012-05-29T06:03:15Z-
dc.date.available2012-05-29T06:03:15Z-
dc.date.issued1992en_US
dc.identifier.citationNature, 1992, v. 360 n. 6406, p. 737-741en_US
dc.identifier.issn0028-0836en_US
dc.identifier.urihttp://hdl.handle.net/10722/147373-
dc.description.abstractIt has been suggested that Hox genes play an important part in the patterning of limbs, vertebrae and craniofacial structures by providing an ordered molecular system of positional values, termed the Hox code. Little is known about the nature of the signals that govern the establishment and regulation of Hox genes, but retinoic acid can affect the expression of these genes in cell lines and in embryonic tissues. On the basis of experimental and clinical evidence, the hindbrain and branchial region of the head are particularly sensitive to the effects of retinoic acid, but the phenotypes are complex and hard to interpret, and how and if they relate to Hox expression has not been clear. Here we follow the changes induced by retinoic acid to hindbrain segmentation and the branchial arches using transgenic mice which contain lacZ reporter genes that reveal the endogenous segment restricted expression of the Hox-B1 (Hox-2.9), Hox-B2 (Hox-2.8) and Krox-20 genes. Our results show that these genes rapidly respond to exposure to retinoic acid at preheadfold stages and undergo a progressive series of changes in segmental expression that are associated with specific phenotypes in hindbrain of first branchial arch. Together the molecular and anatomical alterations indicate that retinoic acid has induced changes in the hindbrain Hox code which result in the homeotic transformation of rhombomeres (r) 2/3 to an r4/5 identity. A main feature of this rhombomeric phenotype is that the trigeminal motor nerve is transformed to a facial identity. Furthermore, in support of this change in rhombomeric identity, neural crest cells derived from r2/3 also express posterior Hox markers suggesting that the retinoic acid-induced transformation extends to multiple components of the first branchial arch.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/natureen_US
dc.relation.ispartofNatureen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAxons - Ultrastructureen_US
dc.subject.meshBranchial Region - Drug Effects - Embryology - Metabolismen_US
dc.subject.meshCell Movement - Drug Effectsen_US
dc.subject.meshDna-Binding Proteins - Geneticsen_US
dc.subject.meshEarly Growth Response Protein 2en_US
dc.subject.meshFacial Bones - Abnormalitiesen_US
dc.subject.meshGene Expression - Drug Effectsen_US
dc.subject.meshGenes, Homeoboxen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Cbaen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshMotor Neurons - Drug Effects - Ultrastructureen_US
dc.subject.meshNeural Crest - Cytologyen_US
dc.subject.meshNeurons, Efferent - Drug Effects - Ultrastructureen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshRhombencephalon - Drug Effects - Embryology - Metabolismen_US
dc.subject.meshSkull - Abnormalitiesen_US
dc.subject.meshTranscription Factors - Geneticsen_US
dc.subject.meshTretinoin - Pharmacologyen_US
dc.titleRetinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identityen_US
dc.typeArticleen_US
dc.identifier.emailSham, MH:mhsham@hkucc.hku.hken_US
dc.identifier.authoritySham, MH=rp00380en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/360737a0en_US
dc.identifier.pmid1361214-
dc.identifier.scopuseid_2-s2.0-0027103903en_US
dc.identifier.volume360en_US
dc.identifier.issue6406en_US
dc.identifier.spage737en_US
dc.identifier.epage741en_US
dc.identifier.isiWOS:A1992KE47200033-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridMarshall, H=7102515675en_US
dc.identifier.scopusauthoridNonchev, S=6603818489en_US
dc.identifier.scopusauthoridSham, MH=7003729109en_US
dc.identifier.scopusauthoridMuchamore, I=6506722537en_US
dc.identifier.scopusauthoridLumsden, A=7102213627en_US
dc.identifier.scopusauthoridKrumlauf, R=7006242495en_US

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