Ectodermal Organ Development Is Regulated by a Signaling Axis.

The developmental role of in ectodermal organs has been characterized using murine knockout models. We generated a conditional over-expression (COEL) mouse to determine the role of expression in epithelial structures at later stages of development after endogenous expression switches to the mesenchyme. over expression (OE) in the oral epithelium creates a new dental epithelial stem cell niche that significantly increases incisor growth. These data indicate that expression is switched off in the dental epithelial at early stages to maintain the stem cell niche and regulate incisor growth. Bioinformatics analyses indicated that expression increased coinciding with decreased expression in the dental epithelium. We generated a murine model over-expressing that targets endogenous expression and -related developmental mechanisms. OE mice have ectodermal organ defects including a lack of incisors, molars, and hair similar to the null mice. OE rescues the OE phenotype demonstrating a critical genetic and developmental role for in the temporal and spatial expression of in epithelial tissues. expression regulates Wnt signaling and Wnt target genes as well as cell proliferation mechanisms, while OE reduced the levels of Wnt target gene expression. The extra stem cell compartment in the mice expressed suggesting that is a stem cell factor, which was absent in the rescue mice. This is the first demonstration of a microRNA OE mouse model that has ectodermal organ defects. These findings demonstrate that the levels of are critical for development and establish a role for in the regulation of ectodermal organ development through the control of expression and an endogenous stem cell niche.