Characterizing the Role of Tspan18 in Neural Crest Development

表征 Tspan18 在神经嵴发育中的作用

基本信息

批准号：
8069128
负责人：
Corinne L. Fairchild
金额：
$ 3.34万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-25 至 2012-05-24
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8069128
关键词：
Address Adhesions Affinity Chromatography Binding Biological Assay Birth Cadherins Cardiac Cell membrane Cleaved cell Co-Immunoprecipitations Complex Congenital Abnormality Data Defect Development Disease Disease Progression Dorsal Embryo Epithelium Evolution Family Family member Goals Health Human Immunohistochemistry In Situ Hybridization Infertility Integral Membrane Protein Integrins Internet Life Malignant Neoplasms Mass Spectrum Analysis Membrane Molecular Mutation Neural Crest Neural Crest Cell Neural tube Neuroblastoma Neuroglia Neurons Nevus Oligonucleotides Peripheral Nervous System Phenotype Play Population Property Proteins Regulation Research Role Scaffolding Protein Signal Pathway Signal Transduction Site Skeleton Snails Specificity Stem cells Structure Surface Tissues Vertebral column Vertebrates cell motility cell type craniofacial glycosylation human PHEMX protein insight knock-down loss of function melanocyte member migration migratory population multipotent cell novel orofacial palmitoylation relating to nervous system scaffold therapy development

项目摘要

DESCRIPTION (provided by applicant): The neural crest is a unique, migratory population of stem cells in vertebrate embryos that gives rise to numerous and varied tissues including the peripheral nervous system, craniofacial skeleton, cardiac outflow tract, and melanocytes. The vast number of disorders caused by deregulation of neural crest development, including birth defects such as orofacial clefts and cancers such as neuroblastoma, reflect the diversity of neural crest derivatives. In spite of the key role played by neural crest cells in development and disease, the mechanisms that control the formation of migratory neural crest cells are poorly understood. My preliminary data identify tetraspanin18 (Tspan18) as a novel, critical regulator of neural crest migratory properties. Tetraspanins are transmembrane proteins that organize and regulate cell signaling, motility, and adhesion. The objective of my research is to characterize the role of Tspan18 in neural crest development. I hypothesize that Tspan18 is part of an essential scaffold responsible for organizing signals at the neural crest cell membrane through interactions with other proteins, and that Tspan18 is required for proper neural crest development. Specifically, the proposed research will characterize the role of Tspan18 in neural crest development by (1) determining the requirement for Tspan18 in the neural crest through antisense morpholino oligonucleotide loss-of-function assays, and (2) identifying potential Tspan18 binding partners by affinity purification and mass spectrometry. My rationale for this proposal is that defining the role of Tspan18 in the neural crest will give us insight into the complex web of signals that coordinates early neural crest development, and may provide clues to understanding the progression of disease, such as neuroblastoma. PUBLIC HEALTH RELEVANCE: Neural crest cells are migrating stem cells that form diverse structures in embryos with backbones. When neural crest cell regulation goes awry, a variety of birth defects and cancers results. This research will characterize a novel protein tetraspanin18 that preliminary evidence suggests is required for neural crest development.

描述（由申请人提供）：神经rest是脊椎动物胚胎中干细胞的独特迁移群，可产生多种组织，包括周围神经系统，颅面骨骼，心脏流出区，心脏流出区和黑素细胞。由神经rest发育引起的大量疾病引起的疾病，包括天生缺陷，例如神经母细胞瘤，例如神经母细胞瘤，反映了神经波峰衍生物的多样性。尽管神经rest细胞在发育和疾病中起着关键作用，但对控制迁移神经rest细胞形成的机制知之甚少。我的初步数据将四叠腺苷18（TSPAN18）识别为神经rest迁移特性的新型，关键的调节剂。四翼烷蛋白是跨膜蛋白，可组织和调节细胞信号传导，运动性和粘附。我的研究的目的是表征TSPAN18在神经波峰发展中的作用。我假设TSPAN18是负责通过与其他蛋白质的相互作用来组织信号的基本支架的一部分，并且TSPAN18是适当的神经波峰发育所必需的。具体而言，拟议的研究将通过（1）通过反义莫菲利诺摩pholino寡核苷酸的功能丧失分析来确定TSPAN18在神经rest中的作用来表征TSPAN18在神经rest发育中的作用，（2）通过亲和力纯化和质量谱图鉴定潜在的TSPAN18结合构件。我对该提案的理由是，定义TSPAN18在神经crest中的作用将使我们深入了解复杂的信号网，这些信号网络坐标了早期神经rest的发展，并可能提供理解疾病进展的线索，例如神经母细胞瘤。公共卫生相关性：神经rest细胞正在迁移干细胞，这些干细胞在带有骨架的胚胎中形成各种结构。当神经rest细胞调节出现问题时，会产生各种出生缺陷和癌症。这项研究将表征一种新型蛋白四质甲酸蛋白酶18的初步证据表明，神经rest发育需要。