Regulation of Functionally-distinct Adhesions and Neuronal Motility

神经系统的功能在很大程度上取决于发育过程中适当连接的形成。 为了完成这项任务，神经元延伸轴突，利用其尖端的动态结构（生长锥）进行导航。 生长锥不能在胚胎中游动：它们沿着粘性表面爬行，只有通过粘附才能前进。 Tosney实验室的成员在理解这些粘连方面取得了关键性的进展，他们发现所有的粘连并不等同。 相反，两种不同类型的粘连调节两种不同的运动结构：“丝状伪足”，作为一个微小的触角状传感器，和“面纱”，传播生长锥向前。 胚胎中的线索可以通过控制这些特殊的粘附来引导生长锥，这些粘附反过来又控制丝状伪足和面纱。 这个项目将测试这些粘连是由不同的分子信号调节的假设。 研究人员将通过实验干扰信号，同时直接观察标记的分子成分，粘附和活生长锥中的运动结构。 由于类似的粘附是所有运动细胞的关键组成部分，这些研究是了解多种细胞类型运动的关键，包括在发育过程中构建生物体的细胞和在转移过程中危及生物体的细胞。除了增进了解外，该项目还直接促进对研究生、本科生和高中生的培训，包括对代表性不足群体的学生的培训。 例如，PI已经培训了36名本科生从事研究工作。 许多人写了荣誉论文，在跨学科的专业会议上介绍了他们的工作，合著出版物，并进入专业培训。 除了在通常的出版物和会议场所传播研究结果外，PI还指导发育生物学教育网站，该网站综合了供公众介绍的教育材料。 拟议的研究项目将继续在多个层次上指导和培训不同的学生研究人员，并向广大受众传播研究成果和哲学。

Nervous system function depends critically on the formation of appropriate connections during development. To accomplish this task, neurons extend axons that navigate using a dynamic structure at their tips, the growth cone. Growth cones do not swim though the embryo: they crawl along sticky surfaces and advance only by making adhesions. A crucial advance toward understanding these adhesions comes from members of the Tosney lab, who discovered that all adhesions are not equivalent. Instead, two distinct types of adhesions regulate two different motile structures: "filopodia" that act as a tiny antennae-like sensors, and "veils" that spread the growth cone forward. Cues in the embryo can guide growth cones by controlling these special adhesions, which in turn control the filopodia and veils. This project will test the hypothesis that these adhesions are regulated by different molecular signals. Researchers will experimentally perturb signals while directly observing labeled molecular components, adhesions and motile structures in live growth cones. Since similar adhesions are crucial components of all moving cells, these studies are key for understanding the movement of multiple cell types, including cells that build the organism during development and cells that endanger the organism during metastasis. In addition to advancing understanding, the project directly promotes training of graduate, undergraduate and high school students, including those of underrepresented groups. For instance, the PI has already trained three dozen undergraduates in research. Many wrote honors theses, presented their work at interdisciplinary professional meetings, coauthored publications, and advanced to professional training. In addition to disseminating findings in the usual venues of publications and meetings, the PI directs the Society for Developmental Biology Education Website which synthesizes education materials for public presentation. The proposed research project will sustain the mentoring and training of diverse student researchers at multiple levels, as well as the dissemination of research findings and philosophies to wide audiences.