The general objective of this proposal is to investigate the role of endocytic trafficking during neural crest development. Neural crest cells are a population of stem-cell-like cells which are present during development and possess the ability to migrate from their place of origin to distinct regions where they give rise to a diverse range o cells types. A large number of human diseases and cancers have been associated with neural crest abnormalities. Additionally, in recent years the neural crest has become a popular model due to its potential for use in regenerative medicine. Therefore, studies of the developmental mechanisms leading to neural crest formation will provide insights into stem cell disorders and cancer and will also aid in discovering potential therapeutic applications for these cells. Recent studies have shown that endocytic trafficking plays an active role in developmental signaling and morphogenesis. Rab (Ras-related proteins in brain) GTPases such as Rab11 and Rab5 are essential members of the endocytic trafficking system and have been implicated in epithelial morphogenesis and cell migration. However, their functions in neural crest cell development have never been directly investigated. Thus, investigating the role of the endocytic pathway in specific developmental processes such as neural crest development will aid not only in understanding embryonic development but will also lead to novel insights which will be invaluable for future studies regarding specific human diseases including cancers. This project aims to evaluate the role of Rab-mediated endocytic trafficking in neural crest cell specification and migration, examine whether endocytosis is polarized in neural crest progenitors and investigate through which signaling pathway endocytic trafficking function during neural crest development.
The findings from this project will lead to a more comprehensive understanding of the role of endocytosis during fundamental process of development such as neural crest development. The results will also be highly significant to the fields of regenerative medicine and cancer research.
