Continuous tooth generation in mouse is induced by activated epithelial Wnt/β-catenin signaling

TLDR

Mammalian teeth normally undergo a single replacement, unlike the continuous replacement seen in many nonmammalian vertebrates and other epithelial organs, which is driven by Wnt signaling. Stabilized β‑catenin in the dental epithelium induces new enamel‑knot signaling centers that bud from existing epithelium, a process that can be reproduced in a computational model by increasing intrinsic activator production, confirming β‑catenin as an upstream activator. Stabilized β‑catenin expression in mouse tooth buds produces dozens of simplified unicusped teeth, indicating that Wnt signaling can trigger tooth renewal—a capability largely lost in mammals with complex tooth morphology.

Abstract

The single replacement from milk teeth to permanent teeth makes mammalian teeth different from teeth of most nonmammalian vertebrates and other epithelial organs such as hair and feathers, whose continuous replacement has been linked to Wnt signaling. Here we show that mouse tooth buds expressing stabilized β-catenin in epithelium give rise to dozens of teeth. The molar crowns, however, are typically simplified unicusped cones. We demonstrate that the supernumerary teeth develop by a renewal process where new signaling centers, the enamel knots, bud off from the existing dental epithelium. The basic aspects of the unlocked tooth renewal can be reproduced with a computer model on tooth development by increasing the intrinsic level of activator production, supporting the role of β-catenin pathway as an upstream activator of enamel knot formation. These results may implicate Wnt signaling in tooth renewal, a capacity that was all but lost when mammals evolved progressively more complicated tooth shapes.