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Article: Requirement for Pbx1 in skeletal patterning and programming chondrocyte proliferation and differentiation

TitleRequirement for Pbx1 in skeletal patterning and programming chondrocyte proliferation and differentiation
Authors
Issue Date2001
PublisherMinistry of Information.
Citation
Development, 2001, v. 128 n. 18, p. 3543-3557 How to Cite?
AbstractPbx1 and a subset of homeodomain proteins collaboratively bind DNA as higher-order molecular complexes with unknown consequences for mammalian development. Pbx1 contributions were investigated through characterization of Pbx1-deficient mice. Pbx1 mutants died at embryonic day 15/16 with severe hypoplasia or aplasia of multiple organs and widespread patterning defects of the axial and appendicular skeleton. An obligatory role for Pbx1 in limb axis patterning was apparent from malformations of proximal skeletal elements, but distal structures were unaffected. In addition to multiple rib and vertebral malformations, neural crest cell-derived skeletal structures of the second branchial arch were morphologically transformed into elements reminiscent of first arch-derived cartilages. Although the skeletal malformations did not phenocopy single or compound Hox gene defects, they were restricted to domains specified by Hox proteins bearing Pbx dimerization motifs and unaccompanied by alterations in Hox gene expression. In affected domains of limbs and ribs, chondrocyte proliferation was markedly diminished and there was a notable increase of hypertrophic chondrocytes, accompanied by premature ossification of bone. The pattern of expression of genes known to regulate chondrocyte differentiation was not perturbed in Pbx1-deficient cartilage at early days of embryonic skeletogenesis, however precocious expression of Col1a1, a marker of bone formation, was found. These studies demonstrate a role for Pbx1 in multiple developmental programs and reveal a novel function in co-ordinating the extent and/or timing of proliferation with terminal differentiation. This impacts on the rate of endochondral ossification and bone formation and suggests a mechanistic basis for most of the observed skeletal malformations.
Persistent Identifierhttp://hdl.handle.net/10722/68151
ISSN
2015 Impact Factor: 6.059
2015 SCImago Journal Rankings: 5.239
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSelleri, Len_HK
dc.contributor.authorDepew, MJen_HK
dc.contributor.authorJacobs, Yen_HK
dc.contributor.authorChanda, Ken_HK
dc.contributor.authorTsang, KYen_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorRubenstein, JLRen_HK
dc.contributor.authorO'Gorman, Sen_HK
dc.contributor.authorCleary, MLen_HK
dc.date.accessioned2010-09-06T06:01:51Z-
dc.date.available2010-09-06T06:01:51Z-
dc.date.issued2001en_HK
dc.identifier.citationDevelopment, 2001, v. 128 n. 18, p. 3543-3557en_HK
dc.identifier.issn0950-1991en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68151-
dc.description.abstractPbx1 and a subset of homeodomain proteins collaboratively bind DNA as higher-order molecular complexes with unknown consequences for mammalian development. Pbx1 contributions were investigated through characterization of Pbx1-deficient mice. Pbx1 mutants died at embryonic day 15/16 with severe hypoplasia or aplasia of multiple organs and widespread patterning defects of the axial and appendicular skeleton. An obligatory role for Pbx1 in limb axis patterning was apparent from malformations of proximal skeletal elements, but distal structures were unaffected. In addition to multiple rib and vertebral malformations, neural crest cell-derived skeletal structures of the second branchial arch were morphologically transformed into elements reminiscent of first arch-derived cartilages. Although the skeletal malformations did not phenocopy single or compound Hox gene defects, they were restricted to domains specified by Hox proteins bearing Pbx dimerization motifs and unaccompanied by alterations in Hox gene expression. In affected domains of limbs and ribs, chondrocyte proliferation was markedly diminished and there was a notable increase of hypertrophic chondrocytes, accompanied by premature ossification of bone. The pattern of expression of genes known to regulate chondrocyte differentiation was not perturbed in Pbx1-deficient cartilage at early days of embryonic skeletogenesis, however precocious expression of Col1a1, a marker of bone formation, was found. These studies demonstrate a role for Pbx1 in multiple developmental programs and reveal a novel function in co-ordinating the extent and/or timing of proliferation with terminal differentiation. This impacts on the rate of endochondral ossification and bone formation and suggests a mechanistic basis for most of the observed skeletal malformations.en_HK
dc.languageengen_HK
dc.publisherMinistry of Information.en_HK
dc.relation.ispartofDevelopmenten_HK
dc.subject.meshAge Factorsen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBody Patterningen_HK
dc.subject.meshBone and Bones - abnormalities - embryologyen_HK
dc.subject.meshBranchial Region - embryologyen_HK
dc.subject.meshCartilage - abnormalities - embryologyen_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCell Divisionen_HK
dc.subject.meshChondrocytes - cytologyen_HK
dc.subject.meshCrosses, Geneticen_HK
dc.subject.meshDNA-Binding Proteins - genetics - metabolismen_HK
dc.subject.meshGenes, Homeoboxen_HK
dc.subject.meshHomeodomain Proteins - genetics - metabolismen_HK
dc.subject.meshHomozygoteen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Knockouten_HK
dc.subject.meshMorphogenesisen_HK
dc.subject.meshOsteogenesisen_HK
dc.subject.meshPhenotypeen_HK
dc.subject.meshProto-Oncogene Proteins - genetics - metabolismen_HK
dc.titleRequirement for Pbx1 in skeletal patterning and programming chondrocyte proliferation and differentiationen_HK
dc.typeArticleen_HK
dc.identifier.emailCheah, KSE:hrmbdkc@hku.hken_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid11566859-
dc.identifier.scopuseid_2-s2.0-0034798317en_HK
dc.identifier.hkuros65348en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034798317&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume128en_HK
dc.identifier.issue18en_HK
dc.identifier.spage3543en_HK
dc.identifier.epage3557en_HK
dc.identifier.isiWOS:000171505200014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridSelleri, L=7004307608en_HK
dc.identifier.scopusauthoridDepew, MJ=9733450300en_HK
dc.identifier.scopusauthoridJacobs, Y=6603570333en_HK
dc.identifier.scopusauthoridChanda, K=8760732600en_HK
dc.identifier.scopusauthoridTsang, KY=22635904200en_HK
dc.identifier.scopusauthoridCheah, KSE=35387746200en_HK
dc.identifier.scopusauthoridRubenstein, JLR=7102359651en_HK
dc.identifier.scopusauthoridO'Gorman, S=6603780895en_HK
dc.identifier.scopusauthoridCleary, ML=7202006199en_HK

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