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: 8484380
• 负责人: Shoba Thirumangalathu
• 金额: $ 14.54万
• 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 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8484380
• 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.

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，但源自局部舌上皮，因此可以被视为改良的上皮附属物。味蕾形成的早期阶段与其他上皮附属物有一些相似之处，即形成称为基板的局部上皮增厚，与下面的间质内陷形成乳头。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，声波刺猬 (SHH) 在味觉器官形态发生中发挥着重要作用。我们最近证明，SHH 后代早期祖细胞群产生了大多数功能性成体味觉细胞类型，并且该胚胎群在出生后丢失。这意味着SHH后代味蕾祖细胞是信号传导中心，它指导味觉祖细胞早期发育和乳头发育后期。在本提案中，我的目的是分别测试 SHH 在味觉祖细胞和乳头发育中的早期和晚期功能。我建议通过利用强大的小鼠分子遗传学工具和诱导性 cre lox 技术结合味觉器官形成的动态延时实时成像来进行这些研究。从味觉器官早期和晚期发育的角度表征 SHH 功能的性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。