Wnt5a regulates growth, patterning, and odontoblast differentiation of developing mouse tooth

TLDR

Wnt/β‑catenin signaling is essential for tooth development beyond the bud stage, yet the role of non‑canonical Wnt signaling in odontogenesis remains poorly understood. The study compared Wnt5a and its receptor Ror2 expression in developing teeth and examined tooth phenotypes in Wnt5a mutants. Expression of Wnt5a and its receptor Ror2 was compared in developing teeth, and tooth phenotypes were analyzed in Wnt5a mutant mice. Wnt5a‑deficient mice exhibited delayed tooth development from E16.5, producing smaller, abnormally patterned teeth with postponed odontoblast differentiation at birth; these defects were linked to increased Axin2 and Shh expression, reduced epithelial and mesenchymal proliferation, and were similarly observed in Ror2 mutants, indicating that Wnt5a regulates growth, patterning, and odontoblast differentiation partly by modulating canonical Wnt/β‑catenin signaling. Published in Developmental Dynamics 240:432–440 (2011); © 2011 Wiley‑Liss, Inc.

Abstract

Abstract Wnt/β‐catenin signaling is essential for tooth development beyond the bud stage, but little is known about the role of non‐canonical Wnt signaling in odontogenesis. Here we compared the expression of Wnt5a, a representative of noncanonical Wnts, with that of Ror2, the Wnt5a receptor for non‐canonical signaling, in the developing tooth, and analyzed tooth phenotype in Wnt5a mutants. Wnt5a ‐deficient mice exhibit retarded tooth development beginning from E16.5, leading to the formation of smaller and abnormally patterned teeth with a delayed odontoblast differentiation at birth. These defects are associated with upregulated Axin2 and Shh expression in the dental epithelium and reduced levels of cell proliferation in the dental epithelium and mesenchyme. Retarded tooth development and defective odontoblast differentiation were also observed in Ror2 mutant mice. Our results suggest that Wnt5a regulates growth, patterning, and odontoblast differentiation during odontogenesis, at least partially by modulating Wnt/β‐catenin canonical signaling. Developmental Dynamics 240:432–440, 2011. © 2011 Wiley‐Liss, Inc.