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microRNA‐26b‐5p Targets Lef‐1 to Regulate Molar and Incisor Development
Author(s) -
Eliason Steven L,
Bustillo Miguel Romero,
Holton Nathan,
Amendt Brad A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.743.11
Subject(s) - wnt signaling pathway , microrna , craniofacial , microbiology and biotechnology , biology , gene isoform , progenitor cell , signal transduction , stem cell , gene , genetics
A microRNA‐26b‐5p ( miR‐26b) over‐expression (OE) mouse was generated to understand the role of miR‐26b during embryonic development. 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 correlation between miR‐26b 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 Wnt signaling, dependent on the Lef‐1 isoform expressed in specific dental tissues. Oral epithelial‐specific overexpression of Lef‐1 can rescue these specific tooth defects. This is the first demonstration of a mouse model for miRNA regulation that has tooth agenesis. miR‐26b regulation of Lef‐1 is essential for normal tooth and craniofacial development.