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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：
8530787
负责人：
Corinne L. Fairchild
金额：
$ 3.39万
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 2013-05-24
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8530787
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）：神经嵴是脊椎动物胚胎中独特的迁移性干细胞群，可产生许多不同的组织，包括外周神经系统、颅面骨骼、心脏流出道和黑素细胞。神经嵴发育失调引起的大量疾病，包括口面裂等出生缺陷和神经母细胞瘤等癌症，反映了神经嵴衍生物的多样性。尽管神经嵴细胞在发育和疾病中起着关键作用，但对控制迁移性神经嵴细胞形成的机制知之甚少。我的初步数据确定tetraspanin18（Tspan18）作为一种新的，关键的调节神经嵴迁移特性。四跨膜蛋白是组织和调节细胞信号传导、运动和粘附的跨膜蛋白。本研究的目的是描述Tspan18在神经嵴发育中的作用。我假设Tspan18是一个重要的支架负责组织信号在神经嵴细胞膜通过与其他蛋白质的相互作用的一部分，Tspan18是必要的适当的神经嵴发育。具体而言，拟议的研究将通过以下方式表征Tspan18在神经嵴发育中的作用：（1）通过反义吗啉代寡核苷酸功能丧失测定确定神经嵴对Tspan18的需求，以及（2）通过亲和纯化和质谱鉴定潜在的Tspan18结合伴侣。我提出这一建议的理由是，确定Tspan18在神经嵴中的作用将使我们深入了解协调早期神经嵴发育的复杂信号网络，并可能为理解疾病的进展提供线索，如神经母细胞瘤。公共卫生相关性：神经嵴细胞是迁移干细胞，在胚胎中形成不同的结构与骨干。当神经嵴细胞的调节出错时，就会导致各种先天缺陷和癌症。这项研究将描述一种新的蛋白质tetraspanin18，初步证据表明这是神经嵴发育所必需的。