Molecular regulation of embryonic taste bud development and differentiation

项目摘要 味蕾是味觉系统的主要感受器官，是传递味觉信息的第一步 到大脑。这些感觉结构包括50-100个神经上皮细胞的异质集合 包括三种形态学类别，它们一起表征味道信息（即甜，苦，酸， 盐、鲜味）转化成神经代码。这些信息直接影响饮食选择，并与以下因素密切相关： 人类的健康和疾病，但尽管它的重要性，我们对味觉系统是如何发展的理解， 并且维持的仍然有限。这项研究的长期目标是揭示分子机制， 调节味蕾发育。以前，我们的实验室已经表明，味觉基板细胞是排他性的味觉， 前体细胞分化成第一个味蕾细胞开始在出生前后;然而， 这个过程还没有被完全理解。在这项研究中，我们将使用成熟的分子遗传学工具， 阐明细胞和分子机制，在发展中的味蕾细胞命运的决定。 使用工程小鼠品系，我们将检查味觉前体细胞在离散阶段的谱系能力 胚胎味蕾发育，使用无偏见的方法来确定决定细胞命运的候选基因 决定在胚胎舌上皮，并评估的作用，声波刺猬信号通路， 调节味觉前体细胞分化的起始。未来的实验，超出了这个补助金的范围， 将重点确定特定的转录调控机制，是必要的和足够的， 味蕾在体内平衡和再生条件下的分化。

Project Summary Taste buds, the primary receptor organs of the gustatory system, are the first step in relaying taste information to the brain. These sensory structures comprise a heterogeneous collection of 50-100 neuro-epithelial cells encompassing three morphological classes that together transduce taste information (i.e. sweet, bitter, sour, salt, umami) into neural code. This information directly influences dietary choice and is intimately linked to human health and disease, yet despite its importance, our understanding of how the taste system is developed and maintained remains limited. The long-term goal of this study is to uncover the molecular mechanisms that regulate taste bud development. Previously, our lab has shown that taste placode cells are exclusive taste precursor cells that differentiate in to the first taste bud cells starting around birth; however, the dynamics of this process are not entirely understood. In this study we will use well-established molecular genetic tools to elucidate the cellular and molecular mechanisms that underlie cell fate decisions within developing taste buds. Using engineered mouse lines, we will examine the lineage capacity of taste precursor cells at discrete stages of embryonic taste bud development, use an unbiased approach to identify candidate genes governing cell fate decisions in the embryonic lingual epithelium, and assess the role of the Sonic hedgehog signaling pathway in regulating the onset of taste precursor cell differentiation. Future experiments, beyond the scope of this grant, will focus on identifying the specific transcriptional regulatory mechanisms that are necessary and sufficient for taste bud differentiation under both homeostatic and regenerative conditions.