Mechanisms of Primary Mesenchyme Morphogenesis

这项提案代表了一个较长期研究计划的试点项目。该计划的长期目标是阐明发育多细胞动物的形态发生机制。这项拟议的工作将研究初级间充质细胞(PMC)的形态发生，PMC是海胆胚胎中的一组迁移细胞。这些细胞经历了一系列戏剧性的运动，可以在活着的胚胎中直接观察到。Ettehsohn博士的研究将把对细胞行为的现场分析与生化和免疫学方法结合起来。具体地说，他将专注于PMC形态发生过程中细胞-细胞和细胞-基质相互作用的三个方面：1)他将结合多种方法研究PMC迁移方向性的机制，包括PMC的微操作、胚胎细胞外基质的分离和修饰(生化和免疫)、细胞消融和电子显微镜，2)他将通过使用抗体和多肽干扰假定的基底层黏附分子的功能，分析PMC与其底物(胚胎基膜)之间发生的分子相互作用，3)他将研究PMC形态发生过程中的细胞-细胞相互作用，集中于PMC阻止胚胎中的其他间充质细胞表达骨骼形成表型的机制。这项建议解决了胚胎发育的一个中心问题：是什么机制负责将细胞组织成高度复杂的组织和器官？众所周知，这一过程涉及广泛的细胞运动和重排。埃滕森博士正在使用发育中的海胆来研究调节这些类型的有序细胞运动的机制。

This proposal represents a pilot project for a longer term research program. The long term goal of the program is an elucidation of morphogenetic mechanisms in developing multicellular animals. The proposed work will examine the morphogenesis of the primary mesenchyme cells (PMCs), a population of migratory cells in the sea urchin embryo. These cells undergo a dramatic sequence of movements that can be observed directly in the living embryo. Dr. Ettehsohn's studies will combine an analysis of cell behavior in situ with biochemical and immunological approaches. Specifically, he will focus on three aspects cell-cell and cell-substratum interactions during PMC morphogenesis: 1) He will examine the mechanisms that underlie the directionality of PMC migration by a combination of approaches, including micromanipulation of PMCs, isolation and modification (biochemical and immunological) of embryonic extracellular matrices, cell ablation, and electron microscopy, 2) He will analyze the molecular interactions that take place between the PMCs and their substratum, the embryonic basal lamina, by using antibodies and peptides to interfere with the function of putative basal lamina adhesion molecules, 3) He will examine cell-cell interactions during PMC morphogenesis, focussing on the mechanism by which the PMCs prevent other mesenchyme cells in the embryo form expressing a skeletogenic phenotype. %%% This proposal addresses a central question of embryonic development: what mechanisms are responsible for organizing cells into highly complex tissues and organs? This process is known to involve extensive cell movements and rearrangements. Dr. Ettensohn is using the developing sea urchin to examine the mechanisms that regulate these types of ordered cell movements.