权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Neuronal regulation of adult taste stem cells

成体味觉干细胞的神经调节

基本信息

批准号：
10350631
负责人：
PeiHua Jiang
金额：
$ 42.17万
依托单位：
MONELL CHEMICAL SENSES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-15 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10350631
关键词：
3-Dimensional Ablation Adenoviruses Adult Ageusia Altered Taste Behavioral Binding Cancer Patient Cell Count Cell Differentiation process Cells Clinical Data Denervation Distant Elderly Epithelial Epithelial Cells Ganglia Generations Genetic Genetic Engineering Genetically Engineered Mouse Glossopharyngeal nerve structure Homeostasis Homologous Gene Immunohistochemistry Impairment In Situ Hybridization In Vitro Individual Knockout Mice LGR5 gene Lead Life Ligands Ligase LoxP-flanked allele Maintenance Malnutrition Modeling Molecular Mus Natural regeneration Nerve Neurons Organ Organoids Patients Perinatal mortality demographics Pharmaceutical Preparations Phenotype Property Proteins Quality of life Radiation therapy Recombinant Proteins Recombinants Recovery Regulation Research Role System Taste Bud Cell Taste Buds Taste Perception Testing Tissues Tongue appetite loss chemotherapy experience gain of function genetic approach improved in vivo intravenous injection loss of function mutant nerve supply nerve transection novel receptor reinnervation self-renewal senescence stem cell differentiation stem cell expansion stem cell proliferation stem cell self renewal stem cells treatment strategy ubiquitin-protein ligase

项目摘要

PROJECT SUMMARY This proposed research will elucidate the molecular basis of neuronal regulation of adult taste stem cells. Taste organs degenerate in the absence of neuronal input, a phenomenon described more than a century ago, but the cellular and molecular mechanisms underlying this are not well defined. We propose to use a combined in vivo and in vitro approach to determine if R-spondin-2 (Rspo2), via interaction of its taste stem cell-expressed receptors Lgr5/Lgr6 and/or Znrf3/Rnf43, is the gustatory-neuron-produced factor that maintains taste bud integrity. In Aim 1, we will determine if Rspo2 is required for taste bud maintenance. Using a loss-of-function approach, conditional ablation of Rspo2 from gustatory neurons that innervate taste tissue will help determine whether gustatory neuron-produced Rspo2 is necessary to maintain taste bud integrity. Conversely, in a gustatory nerve transection model that leads to taste tissue denervation, we will determine if systemically supplied recombinant Rspo2 via adenovirus and purified protein is sufficient for taste cell generation and taste bud regeneration in the absence of gustatory innervation. The loss-of-function and gain-of-function will establish the role of Rspo2 in neuronal regulation of taste tissue maintenance. In Aim 2, we will determine if Rspo2 interacts with its taste stem cell-expressed receptors Lgr5/Lgr6 and/or Znrf3/Rnf43 to regulate taste stem cell activity. We will use genetic approaches, Rspo2 mutants that selectively bind to Lgr5/Lgr6 or Znrf3/Rnf43, taste organoid culture, and gustatory nerve transection to determine how Rspo2 acts. Cancer patients who receive chemotherapy or radiotherapy often experience taste disturbance. The distortion or loss of taste can lead to appetite loss and malnutrition. The mechanisms for drug-induced taste disturbance are not clear, but dysregulation of adult taste stem cell activity could be the culprit. Accomplishing the aims proposed here will be significant steps toward developing strategies for mitigating taste disturbances experienced by individuals who suffer from taste loss or taste distortion.

项目总结