Ishan Mohamed, Wang Zhonghou, Zhao Peng, Yao Yao, Stice Steven, Wells Lance, Mishina Yuji, Liu Hong-Xiang
bioRxiv. 2023 Apr 4:2023.04.03.535414. doi: 10.1101/2023.04.03.535414.
Taste 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 ( ) of using and resulted 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 in vs control. Moreover, we detected a down-regulated epithelial Wnt/β-catenin signaling, and taste papilla development in the was 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.
This is the first set of data to implicate the requirement of tongue mesenchyme in taste papilla cell differentiation.
味蕾是特殊的器官,每个味蕾由容纳味蕾的上皮壁和间充质组织核心组成。在本研究中,我们报告在胚胎发育早期,舌间充质中由1型受体ALK3介导的骨形态发生蛋白(BMP)信号传导对于上皮Wnt/β-连环蛋白活性和味蕾细胞分化是必需的。使用 和 进行间充质特异性敲除( )导致在E12.0时味蕾缺失。生化和细胞分化分析表明,间充质ALK3-BMP信号传导控制以前未被认识的分泌蛋白的产生,即抑制那些抑制作用的蛋白并促进那些促进味觉细胞分化的蛋白。批量RNA测序分析显示,与对照相比, 中舌上皮中差异表达基因(DEG)比间充质中更多。此外,我们检测到上皮Wnt/β-连环蛋白信号传导下调,并且 中的味蕾发育通过GSK3β抑制剂LiCl挽救,但不是Wnt3a。我们的研究结果首次证明了舌间充质在味蕾细胞分化中的必要性。
这是第一组表明舌间充质在味蕾细胞分化中必要性的数据。