Characterizing the essential role of sonic hedgehog in taste bud development

描述（由申请人提供）：味蕾在感觉器官中是独特的，因为它们具有神经元特性，但起源于局部舌上皮，因此可以被认为是修饰的上皮附属物。味蕾形成的早期阶段与其他上皮附属物的形成有一些相似之处，即形成称为基板的局部上皮增厚，其与下面的间充质发生内陷以形成乳头。味蕾在出生时出现在乳头状上皮的顶端。参与上皮附属物形成的类似相互作用信号通路也在味觉器官形态发生中发挥作用。在这些信号分子中，Sonic hedgehog（SHH）在味觉器官的形态发生中起着重要作用。我们最近证明，SHH的后代早期祖细胞群体产生了大多数功能性成人味觉细胞类型，并且这种胚胎群体在出生后丢失。这表明SHH下游味蕾祖细胞是一个信号中心，它指导味觉祖细胞的早期发育和乳头的后期发育。在这个提议中，我的目标是测试SHH的早期和晚期功能的味觉祖细胞和乳头状发育分别。我建议这些研究利用强大的小鼠分子遗传学工具与诱导型cre lox技术结合动态时间推移实时成像味觉器官的形成。在味觉器官的早期和晚期发育方面表征SHH功能的性质是理解味觉器官形成过程中所涉及的分子机制的重要一步。

DESCRIPTION (provided by applicant): Taste buds are unique among sense organs in that they have neuronal properties yet arise from the local lingual epithelium and hence can be considered as modified epithelial appendages. Early stages of taste bud formation share some similarities with those of other epithelial appendages with the formation of a localized epithelial thickening called placode that undergo invagination with the underlying mesenchyme to form a papillae. Taste buds appear at the apices of papillary epithelium around birth. Similar interacting signaling pathways involved in formation of epithelial appendages also play a role in taste organ morphogenesis. Of these signaling molecules, Sonic hedgehog (SHH) has been implicated to play a significant role in taste organ morphogenesis. We recently demonstrated that SHH descendent early progenitor population of cells gives rise to majority of the functional adult taste cell types and this embryonic population being lost postnatally. This implicates that SHH descendent taste bud progenitors are signaling centers, which direct taste progenitor development early and papilla development later. In this proposal, I aim to test the early and late function of SHH in taste progenitor and papillary development respectively. I propose these studies by making use of powerful mouse molecular genetics tools with inducible cre lox technology in combination with dynamic time lapse live imaging of taste organ formation. Characterizing the nature of SHH function in terms of early and late development of taste organs is an important step in understanding molecular mechanisms involved in the process of taste organ formation.