Taste papilla cell differentiation requires tongue mesenchyme via ALK3-BMP signaling to regulate the production of secretory proteins

Abstract

AbstractTaste papillae are specialized organs each of which is comprised of an epithelial wall hosting taste buds and a core of mesenchymal tissue. In the present study, we report that during the early stages of embryonic development, bone morphogenetic protein (BMP) signaling mediated by type 1 receptor ALK3 in the tongue mesenchyme is required for the epithelial Wnt/β-catenin activity and taste papilla cell differentiation. Mesenchyme-specific knockout (cKO) ofAlk3usingWnt1-CreandSox10-Creresulted in an absence of taste papillae at E12.0. Biochemical and cell differentiation analyses demonstrated that mesenchymal ALK3-BMP signaling governs the production of previously unappreciated secretory proteins, i.e., suppresses those that inhibiting and facilitates those promoting taste cell differentiation. Bulk RNA-Sequencing analysis revealed many more differentially expressed genes (DEGs) in the tongue epithelium than in the mesenchyme inAlk3 cKOvs control. Moreover, we detected a down-regulated epithelial Wnt/β-catenin signaling, and taste papilla development in theAlk3 cKOwas rescued by GSK3β inhibitor LiCl, but not Wnt3a. Our findings demonstrate for the first time the requirement of tongue mesenchyme in taste papilla cell differentiation.Summary statementThis is the first set of data to implicate the requirement of tongue mesenchyme in taste papilla cell differentiation.