title: DLX3-Dependent Regulation of Ion Transporters and Carbonic Anhydrases is Crucial for Enamel Mineralization.
abstract: Patients with tricho-dento-osseous (TDO) syndrome, an ectodermal dysplasia caused by mutations in the homeodomain transcription factor DLX3, exhibit enamel hypoplasia and hypomineralization. Here we used a conditional knockout mouse model to investigate the developmental and molecular consequences of Dlx3 deletion in the dental epithelium in vivo. Dlx3 deletion in the dental epithelium resulted in the formation of chalky hypomineralized enamel in all teeth. Interestingly, transcriptomic analysis revealed that major enamel matrix proteins and proteases known to be involved in enamel secretion and maturation were not affected significantly by Dlx3 deletion in the enamel organ. In contrast, expression of several ion transporters and carbonic anhydrases known to play an important role in enamel pH regulation during maturation was significantly affected in enamel organs lacking DLX3. Most of these affected genes showed binding of DLX3 to their proximal promoter as evidenced by chromatin immunoprecipitation sequencing (ChIP-seq) analysis on rat enamel organ. These molecular findings were consistent with altered pH staining evidenced by disruption of characteristic pH oscillations in the enamel. Taken together, these results show that DLX3 is indispensable for the regulation of ion transporters and carbonic anhydrases during the maturation stage of amelogenesis, exerting a crucial regulatory function on pH oscillations during enamel mineralization. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Duverger
authors.affiliation: Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ohara
authors.affiliation: Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Bible
authors.affiliation: Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Zah
authors.affiliation: Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Morasso
mesh_terms: D000566:Amelogenesis; D000818:Animals; D001483:Base Sequence; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003743:Dental Enamel / Q000378:metabolism*; D003746:Dental Enamel Proteins / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D017353:Gene Deletion; D018398:Homeodomain Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019426:Integrases / Q000378:metabolism; D017136:Ion Transport; D018345:Mice, Knockout; D008954:Models, Biological; D009024:Morphogenesis; D011401:Promoter Regions, Genetic; D051381:Rats; D014070:Tooth / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D014074:Tooth Calcification; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: D003746:Dental Enamel Proteins; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C109069:enamel matrix proteins; C045073:Cre recombinase; D019426:Integrases; D002256:Carbonic Anhydrases
keywords: CARBONIC ANHYDRASES; DLX3; ENAMEL MINERALIZATION; ION TRANSPORTERS; PH REGULATION