权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mechanisms of neural crest specification

神经嵴规范的机制

基本信息

批准号：
9764337
负责人：
Sergei Sokol
金额：
$ 47.03万
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：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9764337
关键词：
Actins Actomyosin Address Antibodies Binding Biochemical Biological Biosensor Cell Lineage Cell Nucleus Cells Complex Congenital Abnormality Craniosynostosis Cultured Cells Cytoskeleton Development Disease Disseminated Malignant Neoplasm Ectoderm Ectoderm Cell Embryo Epidermis F-Actin G Actin Gene Activation Gene Expression Gene Targeting Genes Genetic Transcription Goals Intercellular Junctions Knowledge Ligands Link Location Malignant Neoplasms Mediating Mesoderm Metastatic to Modeling Molecular Nervous system structure Neural Crest Neural Crest Cell Neuroectoderm Pathway interactions Peripheral Nervous System Play Post-Translational Protein Processing Prevention Process Proteins Regulation Role Serum Response Factor Signal Induction Signal Transduction Specific qualifier value Stem cells Syndrome System Testing Tissues To specify Transcriptional Activation Transcriptional Regulation Transgenic Organisms WNT Signaling Pathway Wnt proteins Work Xenopus beta catenin blastomere structure cell type craniofacial development embryo tissue experimental study extracellular gene function human disease in vivo insight loss of function myocardin neural plate neurodevelopment neuromechanism novel polymerization progenitor relating to nervous system response stem cell population stem-like cell transcription factor vertebrate embryos

项目摘要

This proposal concerns molecular mechanisms leading to the early development of the vertebrate nervous system, including neural crest cells. The neural crest is a population of stem- cell-like cells, which form in vertebrate embryos at the neural plate border and migrate to diverse locations in the body to give rise to diverse cell types, such as the peripheral nervous system. Neural crest forms as a result of inductive interactions of neuroectoderm, epidermal ectoderm and the underlying mesoderm. The proposed experiments aim to connect cytoskeleton reorganization to neural crest specification. The function of several genes that control actomyosin dynamics will be perturbed to understand the regulatory network that is involved in neural crest formation. These experiments will be carried out in Xenopus embryos, which represent a rapid in vivo system for gene function and allow classical cell biological and biochemical experiments. By connecting upstream regulators, such as Wnt signals, to actin- dependent processes during the initial stages of craniofacial development, the proposed experiments will contribute to the understanding of both the basic developmental mechanisms and are relevant to the disease. A large number of human diseases, such as craniosynostosis, Waardenburg and Hirschsprung's syndromes, and cancer, have been associated with neural crest abnormalities. Studying the mechanisms underlying the development of the neural crest cell should provide insights into human diseases associated with stem cell disorders and cancer.

这一建议涉及导致早期发展的分子机制，脊椎动物神经系统，包括神经嵴细胞。神经嵴是一群- 细胞样细胞，形成于脊椎动物胚胎的神经板边缘，并迁移到在身体的不同位置产生不同的细胞类型，如外周神经系统神经嵴的形成是神经外胚层、表皮外胚层和下面的中胚层。这些实验旨在连接细胞骨架重组到神经嵴特化。一些基因的功能，控制肌动球蛋白动力学将被扰动，以了解调控网络，参与神经嵴的形成这些实验将在非洲爪蟾胚胎中进行，其代表了用于基因功能的快速体内系统，生化实验通过连接上游调节因子，如Wnt信号，肌动蛋白- 在颅面发育的初始阶段，实验将有助于理解这两个基本的发展机制，并且与疾病有关。大量的人类疾病，如颅缝早闭，瓦尔登堡综合征和先天性巨结肠综合征以及癌症与神经系统疾病有关嵴异常研究神经嵴发育的机制细胞应该提供与干细胞疾病相关的人类疾病的见解，癌