Mechanisms of Primary Mesenchyme Morphogenesis

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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.