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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：
7937162
负责人：
LISA A TANEYHILL
金额：
$ 5万
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：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2010-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7937162
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.

我研究生涯的总体主题是确定Wnt的分子基础