microRNA-26b-5p Targets Lef-1 to Regulate Molar and Incisor Development

Objectives: Objective: A microRNA-26b-5p (miR-26b) over-expression (OE) mouse was generated to understand the role of miR-26b during embryonic development.
Methods: Methods: Overexpression of miR-26b in embryonic and postnatal mice was studied by tissue analysis for development/structure, RNA levels and protein levels.
Results: Results: The miR-26b over expression mice have craniofacial defects including a lack of incisors, molars and hair. miR-26b over-expression mice have arrested early tooth development coincident with decreased epithelial progenitor cell proliferation. We demonstrate an inverse coorelation between miR26b levels and lef1 expression in the craniofacial region of these mice. miR-26b targets Lef-1 to modulate Lef-1 transcriptional activity. Both cyclin D1 and c-myc expression are decreased as well as other cell proliferation mechanisms. miR-26b expression correlates with the transition of Lef-1 expression in the dental epithelium. miR-26b regulates all Lef-1 isoforms and alters Wnt signaling in vivo. Oral epithelial-specific overexpression of Lef-1 can rescue these specific tooth defects. This is the first demonstration of a mouse model for miR regulation that has tooth agenesis.

Conclusions: Conclusions: miR-26b regulation of Lef-1 is essential for normal tooth and craniofacial development.