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，是传递味觉信息的第一步 对大脑的影响。这些感觉结构由50-100个神经上皮细胞组成的异质集合 包括共同传递味道信息的三个形态类别(即，甜、苦、酸， 盐，鲜肉)转化成神经代码。这种信息直接影响饮食选择，并与 人类的健康和疾病，尽管它很重要，但我们对味觉系统是如何发展的理解 和维护仍然是有限的。这项研究的长期目标是揭示 调节味蕾发育。此前，我们的实验室已经证明味觉胎盘细胞是独一无二的味觉 从出生前后开始分化为第一个味蕾细胞的前体细胞；然而， 这一过程还没有完全被理解。在这项研究中，我们将使用成熟的分子遗传学工具 阐明决定味蕾发育过程中细胞命运的细胞和分子机制。 利用基因工程小鼠品系，我们将检验味觉前体细胞在不同阶段的谱系能力 对于胚胎味蕾发育，使用一种公正的方法来确定控制细胞命运的候选基因 在胚胎舌上皮中的决定，并评估Sonic Hedgehog信号通路在 调节味觉前体细胞分化的启动。未来的实验，超出了这笔拨款的范围， 将专注于确定特定的转录调控机制，这些机制对于 在稳态和再生条件下的味蕾分化。

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.