Characterizing the essential role of sonic hedgehog in taste bud development

描述(申请人提供)：味蕾在感觉器官中是独一无二的，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改后的上皮性附属物。味蕾形成的早期阶段与其他上皮性附属物的形成有一些相似之处，形成了一种被称为胎盘的局部性上皮增厚，它与下面的间质内陷形成乳头。味蕾出现在出生前后乳头状上皮的顶端。参与上皮性附属器形成的类似的相互作用的信号通路也在味觉器官的形态发生中发挥作用。在这些信号分子中，Sonic hedgehog(SHH)被认为在味觉器官形态发生中起重要作用。我们最近证实，SHH后代的早期祖细胞群体产生了大多数功能性的成人味觉细胞类型，而这些胚胎群体在出生后就消失了。这意味着SHH后代的味蕾前体是信号中心，它早期指导味觉前体的发育，后期指导乳头的发育。在这项建议中，我的目的是分别测试SHH在味觉前体和乳头发育中的早期和晚期功能。我利用强大的小鼠分子遗传学工具和可诱导的cre lox技术，结合味觉器官形成的动态延时实时成像，提出了这些研究。从味觉器官发育的早期和晚期来表征SHH功能的本质，是理解味觉器官形成过程中涉及的分子机制的重要一步。 与公共健康相关：味蕾形成的分子机制是有限的。味蕾的适当组织是至关重要的，因为这会改变个人的味觉，最终影响饮食、生活方式和健康。这项研究将解决分泌信号分子Sonic hedgehog在味觉器官形态发生中的重要作用，并将对调节这一重要感觉系统发育的分子信号的有限知识做出重大贡献。此外，了解胚胎味觉器官的起源将有助于深入了解成熟的味觉系统功能。

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. PUBLIC HEALTH RELEVANCE: Molecular mechanisms governing taste bud formation is limited. Proper organization of taste bud is essential as this alters individual's taste perception, ultimately affecting diet, lifestyle and health. Studies in this proposal will address the essential role of a secreted signaling molecule, Sonic hedgehog in taste organ morphogenesis and will represent a significant contribution to the limited knowledge of molecular signals regulating the development of this important sensory system. Further, understanding the genesis of embryonic taste organs will thus provide insight into mature taste system function.