Taste organs: formation and regulation

项目摘要/摘要 味蕾细胞，将化学刺激转化为神经信号的感觉末端器官，传递给 中枢神经系统，驻留在哺乳动物舌部的味觉乳头中。因此，品尝乳突的主人 分化为包括味蕾细胞的上皮细胞。然而，味觉生物学领域缺乏一个完整的 理解：(1)在乳头发育中什么是可能的味觉细胞前体；(2)如何以及何时 前体在舌上皮中分化，获得味觉乳头和味蕾细胞表型； 潜在的间充质如何以及通过什么因素向乳头和味蕾中的舌上皮传递信号 发展。 神经脊源性细胞在舌上皮中的分布和表型的初步数据 间充质NCDCs的遗传修饰引起的舌头和味觉乳头的改变 在味觉器官的形成中，神经脊对上皮和间充质都有贡献。Cre介导的， 组织特异性的遗传标记和修饰为这些细胞谱系分析和 功能分析。两个用于神经脊分析的转基因小鼠品系，WNT1-和P0-Cre， 都被使用过。我们发现：(1)在舌上皮细胞中，P0-Cre标记的NCDCs首先分布在单个舌上皮细胞中， 在味觉乳头和味蕾中，E11.5-12.5处的元素散在分布，随后形成簇状图案。的本土化 味蕾中P0-Cre标记细胞提示味觉细胞的神经脊来源。我们建议单曲， 散在的P0-Cre标记的上皮细胞是神经脊的前体细胞，它们将经历细胞分化以 味觉乳头和味蕾中的特定细胞类型。(2)在舌间充质中，WNT1和P0-Cre均被标记 NCDC与味觉乳头和味蕾密切相关。WNT1和P0-CRE驱动，条件遗传 I型受体Alk2对骨形态发生蛋白(BMPs)的修饰并显著改变 舌和味觉乳头的发育，提示舌间充质通过BMP信号相互作用 乳头分化时有覆盖的上皮组织。 拟议的研究将解决味觉乳头器官形成的基本问题，使用现代 技术(Cre介导的遗传修饰)以及体内和体外研究的结合。我们的目标是 目的：(目标1)证明神经脊细胞在哪里以及何时迁移到舌或舌原基上皮； 这些细胞如何以及何时在舌上皮中分化以获得特定的细胞表型；哪些类型和 味蕾细胞的比例来自神经脊；(目标2)描述舌间充质是如何， 通过间充质NCDCs中特定受体的BMP信号，与上覆上皮细胞相互作用 舌象和味觉乳突的发育。 总体而言，为证明细胞起源、分化和间充质相互作用而建议的研究 味乳头和味蕾将有助于理解味觉器官的发育，并将带来新的 该领域的信息和新视角对味觉乳突和味蕾细胞的神经隆起的贡献。 关键词：舌；味觉乳头；神经沟衍生细胞

Project Summary/Abstract Taste bud cells, the sensory end organs that transduce chemical stimuli into neural signals conveyed to the central nervous system, reside in taste papillae in the mammalian tongue. Therefore, taste papillae host the epithelium that will differentiate to include taste bud cells. However, the field of taste biology lacks a complete understanding of: (1) what constitutes possible taste cell precursors in developing papillae; (2) how and when the precursors differentiate in lingual epithelium to acquire taste papilla and taste bud cell phenotypes; and (3) how and via what factors the underlying mesenchyme signals to tongue epithelium in papilla and taste bud development. Our preliminary data on neural crest derived cell (NCDC) distributions in lingual epithelium, and of phenotypic alterations of tongue and taste papillae induced by genetic modifications in mesenchymal NCDCs, suggest neural crest contributions to both epithelium and mesenchyme in the formation of taste organs. Cre-mediated, tissue-specific, genetic labeling and modifications provide powerful tools for these cell lineage assays and functional analyses. Two well-characterized transgenic mouse lines for neural crest assays, Wnt1- and P0-Cre, are used. We have found that: (1) In tongue epithelium, P0-Cre labeled NCDCs are first distributed in single, scattered elements at E11.5-12.5 to a clustered pattern later in taste papillae and taste buds. The localization of P0-Cre labeled cells in taste buds indicate a neural crest derivation of taste cells. We propose that the single, scattered P0-Cre labeled epithelial cells are neural crest precursors and these will undergo cell differentiation to specific cell types in taste papillae and taste buds. (2) In tongue mesenchyme, both Wnt1- and P0-Cre labeled NCDCs are closely associated with taste papillae and taste buds. Wnt1- and P0-Cre driven, conditional genetic modifications of type I receptor Alk2 for bone morphogenetic proteins (BMPs) and significantly alter the development of tongue and taste papillae, suggesting that tongue mesenchyme, via BMP signaling, interacts with the overlying epithelium in papilla differentiation. The proposed studies will address fundamental issues about formation of the taste papilla organ, using modern techniques (Cre-mediated genetic modifications) and combination of in vivo and in vitro studies. Our goals are to: (Aim 1) demonstrate where and when neural crest cells migrate to the epithelium of tongue or primordium; how and when these cells differentiate in lingual epithelium to acquire specific cell phenotypes; what types and proportions of taste bud cells are derived from neural crest; (Aim 2) characterize how the tongue mesenchyme, via BMP signaling through specific receptors in mesenchymal NCDCs, interacts with the overlying epithelium in the development of tongue and taste papillae. Overall, the proposed studies for demonstration of cell origin, differentiation and mesenchymal interactions in taste papillae and taste buds will contribute to understanding development of the taste organ and will bring new information and novel perspectives to the field for neural crest contributions to taste papillae and taste bud cells. Key words: tongue; taste papillae; neural crest derived cells