Functional Roles of Wnt and Snail2 Target Genes in Neural Crest Development

Wnt 和 Snail2 靶基因在神经嵴发育中的功能作用

基本信息

批准号：
8051025
负责人：
LISA A TANEYHILL
金额：
$ 0.86万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2010-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8051025
关键词：
Affect Biochemical Biological Biological Assay Cancerous Candidate Disease Gene Cell Adhesion Molecules Cells Collection Defect Development Disease Dorsal Ectoderm Embryo Embryonic Development Embryonic Structures Emigrations Face Future Gene Expression Gene Targeting Generations Genes Genomics Head Human Human Development Human body In Situ Hybridization Investigation Knowledge Malignant Neoplasms Mandibulofacial Dysostosis Mediating Mentors Methods Molecular Molecular Target Mus Nerve Neural Crest Neural Crest Cell Neural tube Normal Cell Pathway interactions Pattern Peripheral Nervous System Phase Pigments Play Postdoctoral Fellow Principal Investigator Process Public Health Regulation Research Research Personnel Role Screening procedure Signal Pathway Signal Transduction Skeleton Skin Specific qualifier value Structure Syndrome Testing Tissues base bone career cell type craniofacial epithelial to mesenchymal transition gene function in vivo insight loss of function melanocyte migration migratory population multipotent cell novel research study slug

项目摘要

The general theme of my research career has been to determine the molecular basis by which the Wnt signaling pathway activates expression of target genes and subsequently affects the generation of a particular cell type, in a context-dependent and temporal manner. The Wnt signaling pathway and its components are used reiteratively throughout embryonic development and in mature tissues during the transformation of normal cells to cancerous ones, demonstrating the importance of this pathway. Wnt signaling plays a significant role in the development of the neural crest, a population of migratory cells that helps pattern the embryo. Because of its contribution to embryonic structures, defects in neural crest development give rise to multiple syndromes, diseases, and cancers, including Axenfeld-Rieger, Di George and Treacher-Collins syndromes, and neurofibromatosis. To further understand how Wnt signaling regulates neural crest development, I have performed a screen to identify novel targets of Wnt signaling involved in this process. Furthermore, investigation into the role of known Wnt target genes, such as Snail2 (Slug) allows me to elucidate how Snail2 regulates expression of its molecular targets in the context of neural crest development. Embryological and biochemical methods will be employed to determine the functional significance of these targets and their mode of regulation by Wnt. Overall, these approaches will provide me with a group of candidate molecules that will likely function in the generation of structures derived from the neural crest, such as the craniofacial skeleton and peripheral nervous system, as well as provide insight into the development of neural crest-derived cancers. In summary, my long-term research and career objectives include conducting mentored research (in the final years of my postdoc) and independent research (as a principal investigator) to elucidate the molecular mechanism underlying Wnt signaling during the development of the neural crest, and applying this knowledge to human development as a whole. This research is relevant to public health because of the biological significance of the neural crest to the proper formation of human bodies, such as the bones of the face, nerves and skin pigment cells. How neural crest cells properly become such diverse structures can help us comprehend what happens when neural crest development is impaired, and human syndromes and cancers arise.

我研究生涯的总主题是确定 Wnt 的分子基础信号通路激活靶基因的表达并随后影响特定的细胞类型，以上下文相关和时间的方式。 Wnt信号通路及其在整个胚胎发育过程中以及在成熟组织中重复使用这些成分正常细胞向癌细胞的转化，证明了该途径的重要性。 Wnt 信号传导在神经嵴的发育中起着重要作用，神经嵴是一群迁移细胞，帮助胚胎形成图案。由于其对胚胎结构的贡献，神经嵴缺陷发育会导致多种综合症、疾病和癌症，包括 Axenfeld-Rieger、Di George 特雷彻-柯林斯综合征和神经纤维瘤病。进一步了解Wnt信号如何调节神经嵴发育过程中，我进行了筛选，以确定参与神经嵴发育的 Wnt 信号传导的新靶点这个过程。此外，研究已知 Wnt 靶基因的作用，例如 Snail2 (Slug) 让我能够阐明 Snail2 如何在神经嵴背景下调节其分子靶点的表达发展。将采用胚胎学和生化方法来确定功能这些目标的重要性及其 Wnt 的调节模式。总的来说，这些方法将为我提供与一组候选分子，这些分子可能会在衍生自的结构的生成中发挥作用神经嵴，例如颅面骨骼和周围神经系统，以及提供对神经嵴衍生癌症的发展。总而言之，我的长期研究和职业目标包括进行指导性研究（在我博士后的最后几年）和独立研究（作为首席研究员）阐明 Wnt 信号传导过程中的分子机制神经嵴的发育，并将这些知识应用于整个人类的发育。这项研究与公共卫生相关，因为神经嵴对人类健康具有重要的生物学意义。人体的正常形成，如面部骨骼、神经和皮肤色素细胞。如何神经嵴细胞适当地变成如此多样化的结构可以帮助我们理解当神经嵴发育受到损害，人类综合症和癌症就会出现。