Mechanisms of neural crest specification

神经嵴规范的机制

• 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
• 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

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。 脊椎动物的神经系统，包括神经脊细胞。神经脊是一群干细胞- 在脊椎动物胚胎的神经板边缘形成的类细胞，并迁移到 身体中的不同位置会产生不同类型的细胞，如周围神经 系统。神经脊的形成是神经外胚层、表皮诱导作用的结果 外胚层和下层中胚层。拟议中的实验旨在将 细胞骨架重组符合神经脊规范。几个基因的功能 控制肌动球蛋白的动力学将被扰动，以了解调控网络，即 参与了神经峰的形成。这些实验将在非洲爪哇胚胎中进行， 它代表了一个快速的体内基因功能系统，并允许经典的细胞生物学和 生化实验。通过将上游调节器，如WNT信号，连接到肌动蛋白- 在头面部发育的初始阶段的依赖过程，建议 实验将有助于理解这两种基本的发育机制 与这种疾病有关。人类的大量疾病，如颅缝闭锁， Waardenburg和Hirschsprung综合征以及癌症与神经性疾病有关 冠部异常。神经脊发育机制的研究 细胞应该为人类与干细胞疾病相关的疾病提供洞察力 癌症。