Cell Interactions and Cell Fate Specification

这项研究计划的长期目标是阐明在早期胚胎发生过程中控制细胞命运的细胞相互作用机制。 胚胎细胞之间的信号传递是所有多细胞动物中细胞命运特化的基本机制。 了解早期胚胎中细胞间的相互作用不仅需要分析信号传导的分子基础，还需要了解胚胎中这种相互作用的细胞背景。 考虑到这些目标，拟议的研究计划涉及细胞和分子方法的整合。 私家侦探将把这些实验策略应用于发育中的海胆胚胎，这是一个可操作的光学透明实验系统。 他计划将重点放在胚胎中两个主要的中胚层细胞群体，初级和次级间充质细胞（PMC和SMC）之间发生的关键调节相互作用上。 PMC在原肠胚形成过程中传递信号，抑制SMC的骨骼发生潜力，并指导这些细胞进入另一种发育程序。 这种相互作用在SMC命运的规范和骨骼发育过程中起着重要作用，并作为模型系统，以研究胚胎调控和细胞信号在早期胚胎。 PMC-SMC相互作用的三个关键方面有待解决：（1）研究活胚胎中细胞命运转换动力学的新方法的发展;（2）PMC信号传导的性质和分子基础;以及（3）响应SMC的性质。 这项拟议中的研究将大大推进我们对发育生物学中心问题的理解。 此外，该研究计划将继续支持在本科，研究生和博士后水平的年轻发育生物学家的培训和发展。

The long term objective of this research program is to elucidate the mechanisms of cell interactions that control cell fates during early embryogenesis. Signaling between embryonic cells is a fundamental mechanism of cell fate specification in all multicellular animals. An understanding of cell-cell interactions in the early embryo will require not only an analysis of the molecular basis of the signaling, but also an understanding of the cellular context of such interactions within the embryo. With these goals in mind, the proposed research program involves an integration of cellular and molecular methodologies. The P.I. will apply these experimental strategies to the developing sea urchin embryo, a manipulable, optically transparent experimental system. He plans to focus on a key regulatory interaction that occurs between the two principal populations of mesodermal cells in the embryo, primary and secondary mesenchyme cells (PMCs and SMCs). PMCs transmit a signal during gastrulation that suppresses the skeletogenic potential of SMCs and directs these cells into an alternative developmental program. This interaction plays an important role in the specification of SMC fates and the process of skeletogenesis, and serves as a model system to study embryonic regulation and cell signalling in the early embryo. Three key aspects of the PMC-SMC interaction are to be addressed: (1) the development of new methods for studying the dynamics of cell fate-switching in living embryos; (2) the properties and molecular basis of PMC signaling; and (3) the properties of the responding SMCs. The proposed research will significantly advance our understanding of a central issue in developmental biology. In addition, this research program will continue to support the training and development of young developmental biologists at the undergraduate, graduate, and postdoctoral levels.