Characterizing the essential role of sonic hedgehog in taste bud development

描述声波刺猬在味蕾发育中的重要作用

• 批准号: 8165929
• 负责人: Shoba Thirumangalathu
• 金额: $ 15.3万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8165929
• 关键词: Address; Adult; Affect; Alleles; Anterior; Automobile Driving; Birth; Cell physiology; Cells; Complex; Development; Diet; Disease; Embryo; Epithelial; Epithelium; Erinaceidae; Fungiform Papilla; Genetic; Genetic screening method; Health; Image; In Vitro; Individual; Knock-out; Knowledge; Life; Life Style; Link; Mediating; Mesenchymal; Mesenchyme; Mitosis; Molecular; Molecular Genetics; Monitor; Morphogenesis; Mus; Nature; Neurons; Organ; Papillary; Phase; Play; Population; Pregnancy; Process; Property; Receptor Cell; Regulation; Role; Sense Organs; Signal Pathway; Signal Transduction; Signaling Molecule; Specific qualifier value; Staging; Stem cells; Structure; System; Taste Buds; Taste Perception; Technology; Testing; Time; Tissues; To specify; Tongue; Wild Type Mouse; appendage; cell behavior; cell type; in vivo; insight; molecular marker; morphogens; postnatal; progenitor; research study; sensory system; tongue papilla; tool

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.

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。 公共卫生相关性：控制味蕾形成的分子机制是有限的。味蕾的适当组织是必不可少的，因为这会改变个人的味觉，最终影响饮食，生活方式和健康。这项提案中的研究将解决分泌的信号分子，声刺猬在味觉器官形态发生中的重要作用，并将代表对调节这一重要感觉系统发育的分子信号的有限知识的重大贡献。此外，了解胚胎味觉器官的发生将为了解成熟的味觉系统功能提供帮助。