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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.

该提案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。神经嵴是一群干细胞细胞样细胞，在神经板边界的脊椎动物胚胎中形成并迁移到身体的不同位置产生不同的细胞类型，例如周围神经系统。神经嵴的形成是神经外胚层、表皮层诱导相互作用的结果外胚层和下面的中胚层。拟议的实验旨在连接细胞骨架重组为神经嵴规范。几个基因的功能控制肌动球蛋白动力学将受到干扰，以了解调节网络参与神经嵴的形成。这些实验将在爪蟾胚胎中进行，它代表了基因功能的快速体内系统，并允许经典的细胞生物学和生化实验。通过连接上游调节器，如Wnt信号，以行动颅面发育初始阶段的相关过程，建议实验将有助于理解这两种基本的发育机制并且与疾病有关。人类的大量疾病，如颅缝早闭、瓦登堡综合征、先天性巨结肠综合征以及癌症与神经系统相关嵴异常。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症。