Endocytic Trafficking in Neural Crest Development

神经嵴发育中的内吞转运

基本信息

批准号：
8954978
负责人：
Andriani Ioannou
金额：
$ 2.15万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-15 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8954978
关键词：
Behavior Biochemical Brain Cartilage Cell Adhesion Molecules Cell Polarity Cell Shape Cells Characteristics Connective Tissue Development Developmental Process Disease Early Endosome Embryo Embryonic Development Embryonic Induction Endocytosis Endosomes Epithelial Experimental Models Future Genetic Guanosine Triphosphate Phosphohydrolases Image Lead Life Link Location Malignant Neoplasms Mediating Membrane Membrane Fusion Membrane Protein Traffic Mesenchymal Modeling Morphogenesis Movement Neoplasm Metastasis Neural Crest Neural Crest Cell Neuroglia Neurons Pathway interactions Peripheral Play Process Property Proteins RAS Superfamily Proteins Recycling Regenerative Medicine Regulation Role Signal Pathway Signal Transduction Stem cells System Testing Therapeutic Tissues Vesicle Xenopus laevis anticancer research base bone cell fate specification cell motility cell type embryo tissue epithelial to mesenchymal transition human disease in vivo insight loss of function melanocyte member migration neural plate novel planar cell polarity prevent progenitor public health relevance rab GTP-Binding Proteins research study stem cell population trafficking vertebrate embryos

项目摘要

DESCRIPTION (provided by applicant): The general objective of this proposal is to investigate the role of endocytic trafficking during neural crest development. Neural crest cells are a population of stem-cell-like cells which are present during development and possess the ability to migrate from their place of origin to distinct regions where they give rise to a diverse range o cells types. A large number of human diseases and cancers have been associated with neural crest abnormalities. Additionally, in recent years the neural crest has become a popular model due to its potential for use in regenerative medicine. Therefore, studies of the developmental mechanisms leading to neural crest formation will provide insights into stem cell disorders and cancer and will also aid in discovering potential therapeutic applications for these cells. Recent studies have shown that endocytic trafficking plays an active role in developmental signaling and morphogenesis. Rab (Ras-related proteins in brain) GTPases such as Rab11 and Rab5 are essential members of the endocytic trafficking system and have been implicated in epithelial morphogenesis and cell migration. However, their functions in neural crest cell development have never been directly investigated. Thus, investigating the role of the endocytic pathway in specific developmental processes such as neural crest development will aid not only in understanding embryonic development but will also lead to novel insights which will be invaluable for future studies regarding specific human diseases including cancers. This project aims to evaluate the role of Rab-mediated endocytic trafficking in neural crest cell specification and migration, examine whether endocytosis is polarized in neural crest progenitors and investigate through which signaling pathway endocytic trafficking function during neural crest development.

描述（由申请人提供）：该提案的总体目标是研究内吞运输在神经嵴发育过程中的作用。神经嵴细胞是一群干细胞样细胞，它们在发育过程中存在，并具有从其起源地迁移到不同区域的能力，在不同区域产生多种细胞类型。许多人类疾病和癌症都与神经嵴异常有关。此外，近年来，神经嵴由于其在再生医学中的应用潜力而成为一种流行的模型。因此，对导致神经嵴形成的发育机制的研究将为干细胞疾病和癌症提供见解，也将有助于发现这些细胞的潜在治疗应用。最近的研究表明，内吞运输在发育信号传导和形态发生中发挥着积极作用。 Rab（大脑中的 Ras 相关蛋白）GTP 酶（例如 Rab11 和 Rab5）是内吞运输系统的重要成员，并且与上皮形态发生和细胞迁移有关。然而，它们在神经嵴细胞发育中的功能从未被直接研究过。因此，研究内吞途径在特定发育过程（例如神经嵴发育）中的作用不仅有助于理解胚胎发育，而且还将带来新的见解，这对于未来有关包括癌症在内的特定人类疾病的研究具有无价的价值。该项目旨在评估 Rab 介导的内吞转运在神经嵴细胞规范和迁移中的作用，检查内吞作用在神经嵴祖细胞中是否极化，并研究神经嵴发育过程中内吞转运通过哪些信号通路发挥作用。