Functional analysis of draxin in cranial neural crest emigration

draxin在颅神经嵴移出中的功能分析

• 批准号: 9391932
• 负责人: Erica Hutchins
• 金额: $ 0.06万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9391932
• 关键词: Address; Affect; Apoptosis; Autonomic ganglion; Biological Assay; Cartilage; Cells; Cephalic; Chick Embryo; Cleaved cell; Cleft Palate; Confocal Microscopy; Coupled; Craniofacial Abnormalities; Data; Defect; Destinations; Development; DiGeorge Syndrome; Disease; Distant; Dorsal; Ectoderm; Embryo; Emigrations; Etiology; Event; Face; Future; Generations; Genes; Goals; Head; Histone H3; Image; In Situ; Knowledge; Lead; Ligation; Light; Link; Literature; Location; Mandibulofacial Dysostosis; Mediating; Morphogenesis; Multipotent Stem Cells; Mutation; Names; Neural Crest; Neural Crest Cell; Neural tube; Neuraxis; Pathway interactions; Pattern; Peripheral Nervous System; Play; Population; Regulation; Reporter; Role; Sensory Ganglia; Signal Pathway; Signal Transduction; Skeleton; Skin Pigmentation; Specific qualifier value; Stem cells; Structure; Time; Translational Research; Vertebrates; WNT Signaling Pathway; attenuation; cell motility; craniofacial; epithelial to mesenchymal transition; experimental study; in vivo; knock-down; loss of function; malformation; migration; neural plate; progenitor; programs; protein protein interaction; public health relevance; relating to nervous system; spatiotemporal; transcriptome; transcriptome sequencing

PROJECT SUMMARY The neural crest is a multipotent stem cell-like population, unique to vertebrates, that is essential for normal craniofacial morphogenesis. These cells contribute to a wide variety of derivatives, including the craniofacial skeleton and cartilage, sensory and autonomic ganglia of the peripheral nervous system, and pigmentation of the skin. Neural crest progenitors arise at the neural plate border, between neural and non- neural ectoderm, and, after neurulation, reside within the dorsal aspect of the future central nervous system, the neural tube. Neural crest cells then undergo an epithelial-to-mesenchymal transition (EMT) to exit the neural tube, and migrate extensively at times to distant locations. Once they reach their destination, neural crest cells cease their migratory program and differentiate into a wide range of derivatives. The neural crest is indispensable for the development of the face— genetic defects affecting neural crest generation, migration, proliferation, or differentiation, result in numerous diseases and malformations affecting the face, e.g. Treacher Collins syndrome, DiGeorge syndrome, and cleft palate to name a few. Thus, there is a need for basic scientific knowledge regarding the precise mechanisms underlying neural crest development. To this end, the Specific Aims of this Proposal seek to use loss-of-function experiments to: 1) Characterize the role of a gene, draxin, in cranial neural crest fate specification and EMT/migration by RNA sequencing and time-lapse confocal microscopy; and 2) Identify the signaling pathway(s) with which draxin interacts to regulate cranial neural crest development, by fluorescent reporter expression and in situ protein-protein interaction assays. The goal of this Proposal is to identify the mechanism by which draxin regulates cranial neural crest EMT and migration during development. Thus, the results of this Proposal will significantly enhance our understanding of the regulation of cranial neural crest EMT and migration, providing new scientific avenues for translational research applications in the treatment of craniofacial defects.

项目摘要 神经rest是脊椎动物独有的多能干细胞样种群，这对于 正常的颅面形态发生。这些细胞有助于多种导数，包括 外周神经系统的颅面骨骼和软骨，感觉和自主神经节，以及 皮肤色素沉着。神经rest祖细胞在神经元素和非神经元之间出现 神经外胚层，神经化后，居住在未来的中枢神经系统的背侧， 神经管。然后，神经rest细胞经历上皮到间质转变（EMT）以退出 神经管，有时会广泛迁移到遥远的位置。一旦到达目的地，神经 波峰细胞停止了其迁徙计划，并分化为广泛的衍生物。神经rest是 面部发展必不可少 增殖或分化导致许多影响面部的疾病和畸形，例如背叛者 柯林斯综合症，迪科尔特综合症和left裂的味道仅举几例。那需要基本 关于神经rest发展的确切机制的科学知识。 为此，该提案的具体目的试图使用功能丧失实验来： 1）表征基因的作用，戏剧化的作用 RNA测序和延时共聚焦显微镜；和 2）确定戏剧性相互作用以调节颅神经rest发育的信号传导途径， 通过荧光报告基因表达和原位蛋白 - 蛋白质相互作用测定。 该提议的目的是确定戏剧调节颅神经crest的机制 开发过程中的EMT和迁移。这，该提案的结果将大大增强我们的 了解颅神经rest和移民的调节，为新的科学途径提供 翻译研究应用在治疗颅面缺陷方面。