Wnt signaling interacts with Shh to regulate taste papilla development
Wnt signaling interacts with Shh to regulate taste papilla development
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DOI：
10.1073/pnas.0607399104
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发表时间：
2007-02-13
影响因子：
11.1
通讯作者：
Margolskee, Robert F.
中科院分区：
文献类型：
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作者：
Iwatsuki, Ken;Liu, Hong-Xiang;Margolskee, Robert F.
Wnt和Shh信号通路对许多上皮组织的发育和成熟至关重要。这两种途径都在干细胞维持、组织发育和肿瘤发生中发挥作用。然而，哺乳动物系统中这些途径之间的联系尚未得到很好的确立。在这里，我们报道了Shh在真菌状乳头中的表达和正常成熟真菌状乳头的形成依赖于Wnt和P-catenin的信号传导。我们观察到，在小鼠蕈状乳头形成过程中，Shh和Wnt/ β -连环蛋白信号通路的组分在发育的基因位中一起表达。在Lef1或Wnt10b敲除小鼠中，Wnt/ β -catenin信号的消除导致Shh表达下调。此外，在Lef1基因敲除小鼠中，真菌状乳头的大小和数量也大大减少。通过检查培养的胚胎小鼠舌头，我们确定Wnt/ β -连环蛋白信号的激活上调了Shh的表达。我们观察到，在培养的舌外植体中，阻断Shh信号可以增强乳头的形成，并伴随着Wnt/ β -catenin信号的上调，这表明Shh抑制了Wnt/ β -catenin通路。外源添加的Shh抑制内源性Shh的表达并抑制Wnt/ β -catenin信号传导（在TOPGAL小鼠中进行了评估），进一步暗示Shh是Wnt/ β -catenin通路的抑制剂。我们的观察结果表明，Wnt/ β -连环蛋白信号传导以及Writ和Shh通路之间的相互作用在真菌状乳头的发育中起着至关重要的作用。
Wnt and Shh signaling pathways are critical for the development and maturation of many epithelial tissues. Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expression in fungiform papillae and formation of normal mature fungiform papillae depend on signaling through Wnt and P-catenin. We observed that during fungiform papilla formation in mice, Shh and components of the Wnt/beta-catenin signaling pathway are expressed together in the developing placode. The elimination of Wnt/beta-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression. in addition, the size and number of fungiform papillae were greatly reduced in Lef1 knockout mice. By examining embryonic mouse tongues in culture we determined that activation of Wnt/beta-catenin signaling up-regulates Shh expression. We observed that blocking Shh signaling in cultured tongue explants enhanced papillae formation and was accompanied by an up-regulation of Wnt/beta-catenin signaling, indicating that Shh inhibits the Wnt/beta-catenin pathway. Exogenously added Shh suppressed expression of endogenous Shh and inhibited Wnt/beta-catenin signaling (assessed in TOPGAL mice), further implicating Shh as an inhibitor of the Wnt/beta-catenin pathway. Our observations indicate that Wnt/beta-catenin signaling and interactions between the Writ and Shh pathways play essential roles in the development of fungiform papillae.