Temporal Control of WNT Activity Regulates Tooth Number in Fish

Abstract

Wnts determine cell polarity, cell proliferation, and cell differentiation during embryogenesis and play an essential role during tooth development initiation and morphogenesis. Wnt/beta-catenin signaling has a time-dependent role in development because various signaling molecules that mutually interact are involved in the pathway, and tight regulation of the pathway is essential for normal development. Studies investigating how the Wnt/beta-catenin signaling pathway controls the different stages of tooth development are rare. Specifically, the effects of Wnt/beta-catenin signaling loss of function on different stages of tooth development are currently unknown. Here, we report the stage-dependent role of Wnt/beta-catenin signaling in tooth development. In vivo loss and gain of function of Wnt/beta-catenin signaling were implemented through the genetic overexpression of DKK1 with heat shock-inducible transgenic models and the pharmacologic inhibition of beta-catenin destruction complex formation in zebrafish, respectively. We demonstrated that transient inhibition of Wnt/beta-catenin signaling interrupted tooth development in a stage-dependent manner and conditional activation of Wnt/beta-catenin signaling during 4V morphogenesis inhibited the development of 3V. These findings suggest that Wnt/beta-catenin signaling plays an important role in the morphogenesis of teeth and the initiation of sequential tooth development in a stage-dependent manner.