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β-Catenin signaling regulates temporally discrete phases of anterior taste bud development

机译:β-连环蛋白信号传导调节前味蕾发育的时间离散阶段

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摘要

The sense of taste is mediated by multicellular taste buds located within taste papillae on the tongue. In mice, individual taste buds reside in fungiform papillae, which develop at mid-gestation as epithelial placodes in the anterior tongue. Taste placodes comprise taste bud precursor cells, which express the secreted factor sonic hedgehog (Shh) and give rise to taste bud cells that differentiate around birth. We showed previously that epithelial activation of β-catenin is the primary inductive signal for taste placode formation, followed by taste papilla morphogenesis and taste bud differentiation, but the degree to which these later elements were direct or indirect consequences of β-catenin signaling was not explored. Here, we define discrete spatiotemporal functions of β-catenin in fungiform taste bud development. Specifically, we show that early epithelial activation of β-catenin, before taste placodes form, diverts lingual epithelial cells from a taste bud fate. By contrast, β-catenin activation a day later within Shh+ placodes, expands taste bud precursors directly, but enlarges papillae indirectly. Further, placodal activation of β-catenin drives precocious differentiation of Type I glial-like taste cells, but not other taste cell types. Later activation of β-catenin within Shh+ precursors during papilla morphogenesis also expands taste bud precursors and accelerates Type I cell differentiation, but papilla size is no longer enhanced. Finally, although Shh regulates taste placode patterning, we find that it is dispensable for the accelerated Type I cell differentiation induced by β-catenin.
机译:味觉由位于舌头味觉乳头内的多细胞味蕾介导。在小鼠中,单个味蕾驻留在真菌状乳头中,该乳头在妊娠中期以前舌的上皮斑块形成。味蕾包含味蕾前体细胞,它们表达分泌因子声波刺猬(Shh)并产生在出生时分化的味蕾细胞。我们先前表明,β-catenin的上皮激活是味觉斑块形成,其次是味觉乳头形态发生和味蕾分化的主要诱导信号,但这些后来的元素对β-catenin信号产生直接或间接影响的程度并未探索。在这里,我们定义了β-catenin在真菌状味蕾发育中的离散时空功能。具体而言,我们表明,在味觉形成之前,β-catenin的早期上皮激活会转移味蕾命运中的舌上皮细胞。相比之下,一天后在Shh + placode中激活β-catenin,直接使味蕾前体膨胀,但间接使乳头增大。此外,β-catenin的表面活化激活了I型神经胶质样味觉细胞的早熟分化,但没有其他味觉细胞类型。乳头形态发生过程中,Shh + 前体中β-catenin的后期活化也扩大了味蕾前体并加速了I型细胞分化,但乳头大小不再增加。最后,尽管Shh调节味觉平台模式,但我们发现它对于由β-catenin诱导的I型细胞加速分化是必不可少的。

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