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The role of Irf6 in tooth epithelial invagination.

ABSTRACT: Thickening and the subsequent invagination of the epithelium are an important initial step in ectodermal organ development. Ikk? has been shown to play a critical role in controlling epithelial growth, since Ikk? mutant mice show protrusions (evaginations) of incisor tooth, whisker and hair follicle epithelium rather than invagination. We show here that mutation of the Interferon regulatory factor (Irf) family, Irf6 also results in evagination of incisor epithelium. In common with Ikk? mutants, Irf6 mutant evagination occurs in a NF-?B-independent manner and shows the same molecular changes as those in Ikk? mutants. Irf6 thus also plays a critical role in regulating epithelial invagination. In addition, we also found that canonical Wnt signaling is upregulated in evaginated incisor epithelium of both Ikk? and Irf6 mutant embryos.

SUBMITTER: Blackburn J

PROVIDER: S-EPMC7462630 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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The role of Irf6 in tooth epithelial invagination.

Blackburn James J Ohazama Atsushi A Kawasaki Katsushige K Otsuka-Tanaka Yoko Y Liu Bigang B Honda Kenya K Rountree Ryan B RB Hu Yinling Y Kawasaki Maiko M Birchmeier Walter W Schmidt-Ullrich Ruth R Kinoshita Akira A Schutte Brian C BC Hammond Nigel L NL Dixon Michael J MJ Sharpe Paul T PT

Developmental biology 20120214 1

Thickening and the subsequent invagination of the epithelium are an important initial step in ectodermal organ development. Ikkα has been shown to play a critical role in controlling epithelial growth, since Ikkα mutant mice show protrusions (evaginations) of incisor tooth, whisker and hair follicle epithelium rather than invagination. We show here that mutation of the Interferon regulatory factor (Irf) family, Irf6 also results in evagination of incisor epithelium. In common with Ikkα mutants, ...[more]

PMID: 22366192

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Project description:Clefting of the lip, with or without palatal involvement (CLP), is associated with a higher incidence of developmental tooth abnormalities, including hypodontia and supernumerary teeth, aberrant crown and root morphologies, and enamel defects, although the underlying mechanistic link is poorly understood. As most CLP genes are expressed throughout the oral epithelium, the authors hypothesized that the expression of CLP genes may persist in the dental epithelium and thus, in addition to their earlier role in labiopalatine development, may play an important functional role in subsequent tooth patterning and amelogenesis. To address this, the authors generated a unique conditional knockout model involving the major CLP gene, Irf6, that overcomes the previously reported perinatal lethality to enable assessment of any posteruption dental phenotypes. A dental epithelium-specific Irf6 conditional knockout (Irf6-cKO) mouse was generated via a Pitx2-Cre driver line. Dental development was analyzed by microcomputed tomography, scanning electron microscopy, histology, immunohistochemistry, and quantitative polymerase chain reaction. Irf6-cKO mice displayed variable hypodontia, occasional supernumerary incisors and molars, as well as crown and root patterning anomalies, including peg-shaped first molars and taurodontic and C-shaped mandibular second molars. Enamel density was reduced in preeruption Irf6-cKO mice, and some shearing of enamel rods was noted in posteruption incisors. There was also rapid attrition of Irf6-cKO molars following eruption. Histologically, Irf6-cKO ameloblasts exhibited disturbances in adhesion and polarity, and delayed enamel formation was confirmed immunohistochemically. Altered structure of Hertwig's epithelial root sheath was also observed. These data support a role for IRF6 in tooth number, crown and root morphology and amelogenesis that is likely due to a functional role of Irf6 in organization and polarity of epithelial cell types. This data reinforce the notion that various isolated tooth defects could be considered part of the CLP spectrum in relatives of an affected individual.

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The role of Irf6 in tooth epithelial invagination.

Publications

The role of Irf6 in tooth epithelial invagination.

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