Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA 30602, USA.
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Development. 2023 Sep 15;150(18). doi: 10.1242/dev.201838. Epub 2023 Sep 25.
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/β-catenin activity and taste papilla differentiation. Mesenchyme-specific knockout (cKO) of Alk3 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. it 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 Alk3 cKO versus control. Moreover, we detected downregulated epithelial Wnt/β-catenin signaling and found that taste papilla development in the Alk3 cKO was rescued by the GSK3β inhibitor LiCl, but not by Wnt3a. Our findings demonstrate for the first time the requirement of tongue mesenchyme in taste papilla cell differentiation.
味蕾是专门的器官，每个味蕾由上皮壁组成，上皮壁上有味蕾，还有中胚层组织的核心。在本研究中，我们报告了在小鼠胚胎早期味蕾发育过程中，舌间质中 I 型受体 ALK3 介导的骨形态发生蛋白（BMP）信号对于上皮 Wnt/β-连环蛋白活性和味蕾分化是必需的。利用 Wnt1-Cre 和 Sox10-Cre 特异性敲除（cKO）ALK3 导致 E12.0 时味蕾缺失。生化和细胞分化分析表明，间质 ALK3-BMP 信号控制了以前未被认识的分泌蛋白的产生，即抑制那些抑制味蕾分化的蛋白，促进那些促进味蕾分化的蛋白。大规模 RNA-seq 分析显示，ALK3 cKO 与对照相比，舌上皮中的差异表达基因（DEGs）比间质中的多得多。此外，我们检测到上皮 Wnt/β-连环蛋白信号下调，并且发现 Alk3 cKO 中的味蕾发育可以通过 GSK3β 抑制剂 LiCl 挽救，但不能通过 Wnt3a 挽救。我们的研究结果首次证明了舌间质在味蕾细胞分化中的必要性。
