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

我的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，并随后影响一种 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 在整个胚胎发育过程中以及在成熟组织中， 正常细胞转化为癌细胞，证明了这一途径的重要性。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， 帮助胚胎定型由于它对胚胎结构的贡献，神经嵴的缺陷 发展引起多种综合征、疾病和癌症，包括Axene-Rieger、Di乔治 Treacher-Collins综合征和神经纤维瘤病。为了进一步了解Wnt信号是如何调节 神经嵴发育，我已经进行了筛选，以确定新的Wnt信号转导的目标，参与 这个过程此外，研究已知的Wnt靶基因，如Snail 2（Slug） 这使我能够阐明Snail 2如何在神经嵴的背景下调节其分子靶点的表达。 发展胚胎学和生物化学方法将被用来确定功能 这些目标的意义和它们的Wnt调控模式。总的来说，这些方法将为我提供 用一组候选分子，这些分子可能在衍生自 神经嵴，如颅面骨骼和周围神经系统，以及提供洞察 神经嵴源性癌症的发展。总之，我的长期研究和职业目标 包括指导研究（在我博士后的最后几年）和独立研究（作为一个 首席研究员），以阐明Wnt信号转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发育。 这项研究与公共卫生有关，因为神经嵴对大脑的生物学意义。 人体的正常形成，如面部的骨骼、神经和皮肤色素细胞。如何 神经嵴细胞变成如此多样化的结构可以帮助我们理解当 神经嵴发育受损，出现人类综合症和癌症。

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.