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育过程中控制细胞命运的细胞相互作用的机制。胚胎细胞之间的信号传递是决定所有多细胞动物细胞命运的基本机制。要了解早期胚胎中细胞与细胞的相互作用，不仅需要分析信号传递的分子基础，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。P.I.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、光学透明的实验系统。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)之间发生的关键调控相互作用上。原肠系膜细胞在原肠形成过程中传递一种信号，抑制系膜细胞的骨骼生成能力，并引导这些细胞进入另一种发育程序。这种相互作用在SMC命运的决定和骨骼形成过程中起着重要的作用，是研究胚胎调控和早期胚胎细胞信号转导的模型系统。PMC-SMC相互作用的三个关键方面是：(1)研究活胚胎细胞命运转换动力学的新方法的发展；(2)PMC信号的特性和分子基础；(3)响应的SMC的特性。这项拟议的研究将极大地促进我们对发育生物学中的一个核心问题的理解。此外，这项研究计划将继续支持本科生、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.