Role of Chemorepellants during Neural Crest Migration in the Eye

化学排斥剂在眼部神经嵴迁移过程中的作用

• 批准号: 7319677
• 负责人: Peter Y Lwigale
• 金额: $ 8.88万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7319677
• 关键词: Accounting; Animal Model; Anterior; Area; Behavior; Cells; Chimera organism; Collagen Fibril; Cornea; Corneal Endothelium; Data; Defect; Development; Dorsal; Employee Strikes; Endothelium; Environment; Epithelium; Event; Eye; Eye Abnormalities; Eye Development; Faculty; Immigration; In Vitro; Ligands; Modeling; Molecular; Molecular Biology; Mus; Mutant Strains Mice; Mutation; Natural regeneration; Neural Crest; Neural Crest Cell; Neural tube; Neurons; Neuropilin-1; Numbers; Pattern; Phase; Phase Transition; Population; Process; Property; Quail; Reporting; Research; Research Personnel; Role; Semaphorin-3A; Signal Transduction; Stem cells; Techniques; Time; Tissues; Transcript; Video Microscopy; Vision; Visual; Work; Wound Healing; cell behavior; in vivo; insight; lens; migration; monolayer; programs; receptor; research study; spatiotemporal; wound

DESCRIPTION (provided by applicant): Despite of their developmental importance and the striking number of visual defects that arise from aberrant neural crest development, little is known of the molecular signals that control their migration during eye development or during the regeneration of the cornea. In the periocular region, neural crest cells express Neuropilin-1 (Npn-1) prior to their migration into the eye, while the lens expresses SemaphorinSA (SemaSA). Interestingly, Npn-1 and SemaSA are also differentially expressed as the cornea regenerates during wound healing. However the role of Npn-1/SemaSA signaling during eye development and wound healing has not been examined. Therefore it is critical to identify and characterize the role of guidance molecules that regulate the migration of periocular neural crest cells and their keratocyte progeny in the cornea. This project will study the role of Npn-1/SemaSA interactions during neural crest migration in the eye. There will be special emphasis on the invasion of periocular neural crest into the eye rudiment, their interaction with the lens and differentiation into corneal endothelium and stroma, and relationship to neural crest-derived keratocytes during regeneration of the cornea. This proposal combines classical embryological techniques with molecular biology and video microscopy to visualize neural crest migration in real-time and examine the role of Npn-1 and SemaSA during these events. Experiments will be carried out in chick and mouse, as each model offers unique experimental advantages. The following specific aims will be performed: 1) Examine the role of Npn-1/SemaSA interactions during neural crest contribution to the cornea in vivo and in vitro. 2) Examine the migration of neural crest cells into the cornea by in vivo time-lapse video microscopy. 3) Characterize the expression of Npn-1 and SemaSA during mouse eye development. 4) Examine the role of Npn-1/SemaSA interactions during mouse eye development. 5) Examine the role of Npn-1/SemaSA interactions during cornea wound healing. Significance: The proposed research aims to provide an insight into the role of guidance molecules during neural crest migration into the eye during development and of their keratocyte progeny during cornea regeneration. Understanding the role of guidance molecules during -these processes may provide clues on how the migration pattern of neural crest cells is disrupted in congenital eye disorders.

描述（由申请人提供）：尽管其发育重要性和异常神经嵴发育引起的视觉缺陷数量惊人，但对在眼发育或角膜再生期间控制其迁移的分子信号知之甚少。在眼周区域中，神经嵴细胞在迁移到眼睛中之前表达神经纤毛蛋白-1（Npn-1），而透镜表达脑信号蛋白SA（SemaSA）。有趣的是，Npn-1和SemaSA在伤口愈合过程中角膜再生时也有差异表达。然而，Npn-1/SemaSA信号传导在眼睛发育和伤口愈合过程中的作用尚未研究。因此，鉴定和表征调控眼周神经嵴细胞及其角膜细胞后代在角膜中的迁移的引导分子的作用是至关重要的。该项目将研究Npn-1/SemaSA相互作用在眼神经嵴迁移过程中的作用。将特别强调眼周神经嵴侵入眼的雏形，它们与透镜的相互作用和分化成角膜内皮和基质，以及在角膜再生过程中与神经嵴衍生的角膜细胞的关系。该提案将经典的胚胎学技术与分子生物学和视频显微镜相结合，以实时可视化神经嵴迁移，并研究Npn-1和SemaSA在这些事件中的作用。实验将在鸡和小鼠中进行，因为每种模型都提供了独特的实验优势。1）在体内和体外检查神经嵴对角膜的贡献期间Npn-1/SemaSA相互作用的作用。2)通过体内延时视频显微镜检查神经嵴细胞向角膜的迁移。3)表征小鼠眼发育期间Npn-1和SemaSA的表达。4)研究Npn-1/SemaSA相互作用在小鼠眼睛发育过程中的作用。5)检查Npn-1/SemaSA相互作用在角膜伤口愈合过程中的作用。重要性：拟议的研究旨在深入了解神经嵴在发育过程中迁移到眼睛中的指导分子的作用，以及角膜再生过程中角膜细胞后代的作用。了解这些过程中引导分子的作用可能会提供关于先天性眼病中神经嵴细胞迁移模式如何被破坏的线索。