Taste papilla cell differentiation requires the regulation of secretory protein production by ALK3-BMP signaling in the tongue mesenchyme

Taste papillae are specialized organs, each of which comprises an epithelial wall hosting taste buds and a core of mesenchymal tissue. In the present study, we report that during early taste papilla development in mouse embryos, bone morphogenetic protein (BMP) signaling mediated by type 1 receptor ALK3 in the tongue mesenchyme is required for epithelial Wnt/I3-catenin activity and taste papilla differentiation. Mesenchyme-specific knockout (cKO) of Alka using Wnt1-Cre and Sox10-Cre resulted in an absence of taste papillae at E12.0. Biochemical and cell differentiation analyses demonstrated that mesenchymal ALK3-BMP signaling governed the production of previously unappreciated secretory proteins, i.e. suppressed those that inhibit and facilitated those that promote taste papilla differentiation. Bulk RNA-sequencing analysis revealed many more differentially expressed genes (DEGs) in the tongue epithelium than in the mesenchyme in Alka cKO versus control. Moreover, we detected downregulated epithelial Wnt/I3-catenin signaling and found that taste papilla development in the Alka cKO was rescued by the GSK3I3 inhibitor LiCl, but not by Wnt3a. Our findings demonstrate for the first time the requirement of tongue mesenchyme in taste papilla cell differentiation.

Automated summary

This study reveals the importance of bone morphogenetic protein signaling mediated by ALK3 receptor in the differentiation of taste papillae during early embryo development in mice. The study demonstrates that ALK3-BMP signaling in mesenchyme is required for the activation of Wnt/I3-catenin pathway, which promotes taste papilla differentiation. The findings highlight the role of tongue mesenchyme in taste papilla cell differentiation.