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

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，从而影响 特定的单元类型，以依赖于上下文和临时的方式。Wnt信号通路及其相关研究进展 在整个胚胎发育过程中和在成熟组织中 正常细胞向癌细胞的转化，证明了这一途径的重要性。WNT 信号在神经脊的发育中起着重要作用，神经脊是一组迁移细胞，它可以 帮助形成胚胎的模式。由于它对胚胎结构的贡献，神经脊的缺陷 发展会导致多种症状、疾病和癌症，包括阿森菲尔德-里格、迪·乔治 以及Treacher-Collins综合征和神经纤维瘤病。进一步了解Wnt信号是如何调节的 神经脊发育，我已经进行了一次筛选，以确定Wnt信号参与的新靶点 这一过程。此外，对已知的Wnt靶基因的作用进行了研究，如Snail2(Slug) 使我能够阐明Snail2如何在神经脊的背景下调节其分子靶标的表达 发展。将使用胚胎学和生化方法来确定功能 这些目标的意义以及WNT对这些目标的监管模式。总体而言，这些方法将为我提供 具有一组候选分子，这些候选分子可能会在产生源自 神经脊，如头面部骨骼和周围神经系统，以及提供洞察 神经脊源性癌症的发展。总而言之，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 首席研究员)阐明了Wnt信号转导的分子机制 神经脊的发展，并将这一知识应用于人类整体发展。 这项研究与公共健康有关，因为神经脊对 人体的正常构成，如面部骨骼、神经和皮肤色素细胞。多么 神经脊细胞正确地变成这样不同的结构可以帮助我们理解当 神经脊发育受损，出现人类综合征和癌症。

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.