Show simple item record

dc.contributor.authorDuverger, Olivier
dc.contributor.authorZah, Angela
dc.contributor.authorIsaac, Juliane
dc.contributor.authorSun, Hong-Wei
dc.contributor.authorBartels, Anne K.
dc.contributor.authorLian, Jane B.
dc.contributor.authorBerdal, Ariane
dc.contributor.authorHwang, Joonsung
dc.contributor.authorMorasso, Maria I.
dc.date2022-08-11T08:10:57.000
dc.date.accessioned2022-08-23T17:26:15Z
dc.date.available2022-08-23T17:26:15Z
dc.date.issued2012-04-06
dc.date.submitted2012-05-10
dc.identifier.citationJ Biol Chem. 2012 Apr 6;287(15):12230-40. Epub 2012 Feb 20. <a href="http://dx.doi.org/10.1074/jbc.M111.326900">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M111.326900
dc.identifier.pmid22351765
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49595
dc.description.abstractDuring development, Dlx3 is expressed in ectodermal appendages such as hair and teeth. Thus far, the evidence that Dlx3 plays a crucial role in tooth development comes from reports showing that autosomal dominant mutations in DLX3 result in severe enamel and dentin defects leading to abscesses and infections. However, the normal function of DLX3 in odontogenesis remains unknown. Here, we use a mouse model to demonstrate that the absence of Dlx3 in the neural crest results in major impairment of odontoblast differentiation and dentin production. Mutant mice develop brittle teeth with hypoplastic dentin and molars with an enlarged pulp chamber and underdeveloped roots. Using this mouse model, we found that dentin sialophosphoprotein (Dspp), a major component of the dentin matrix, is strongly down-regulated in odontoblasts lacking Dlx3. Using ChIP-seq, we further demonstrate the direct binding of Dlx3 to the Dspp promoter in vivo. Luciferase reporter assays determined that Dlx3 positively regulates Dspp expression. This establishes a regulatory pathway where the transcription factor Dlx3 is essential in dentin formation by directly regulating a crucial matrix protein.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22351765&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M111.326900
dc.subjectTranscription Factors
dc.subjectHomeodomain Proteins
dc.subjectDentin
dc.subjectNeural Crest
dc.subjectOdontoblasts
dc.subjectCell Biology
dc.titleNeural Crest Deletion of Dlx3 Leads to Major Dentin Defects through Down-regulation of Dspp
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume287
dc.source.issue15
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/264
dc.identifier.contextkey2838656
html.description.abstract<p>During development, Dlx3 is expressed in ectodermal appendages such as hair and teeth. Thus far, the evidence that Dlx3 plays a crucial role in tooth development comes from reports showing that autosomal dominant mutations in DLX3 result in severe enamel and dentin defects leading to abscesses and infections. However, the normal function of DLX3 in odontogenesis remains unknown. Here, we use a mouse model to demonstrate that the absence of Dlx3 in the neural crest results in major impairment of odontoblast differentiation and dentin production. Mutant mice develop brittle teeth with hypoplastic dentin and molars with an enlarged pulp chamber and underdeveloped roots. Using this mouse model, we found that dentin sialophosphoprotein (Dspp), a major component of the dentin matrix, is strongly down-regulated in odontoblasts lacking Dlx3. Using ChIP-seq, we further demonstrate the direct binding of Dlx3 to the Dspp promoter in vivo. Luciferase reporter assays determined that Dlx3 positively regulates Dspp expression. This establishes a regulatory pathway where the transcription factor Dlx3 is essential in dentin formation by directly regulating a crucial matrix protein.</p>
dc.identifier.submissionpathstein/264
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages12230-40


This item appears in the following Collection(s)

Show simple item record