It is generally accepted that bending of epithelial cell sheets during early organ formation is caused by constriction of cell apices and/or bases. The mechanism of constriction is thought to be interactions of myosin with actin filaments anchored in the plasma membrane. This hypothesis is based primarily on circumstantial evidence. Changes have been shown in the width of microfilament bundles at cell apices in morphogenetically active regions of primordia and shape change in many organ primordia is inhibited by drugs that interfere with the integrity of actin filaments. However, the arrangement of filament bundles differs in different primordia and in different regions of the same primordium. Careful measurements of shape change have been done only for neural fold formation and the results do not exclude other mechanisms for shape change. The goal of this study is to provide not only careful measurements of cell size and shape for all regions of several representative primordia, but also to quantitate changes in cytoskeletal components during the shape changes. This will be accomplished by computer assisted image analysis. Furthermore, the results will be tested with a computer model of organogenesis to determine which observed changes are sufficient and necessary to produce the organotypic shape changes. Computer modelling will allow additional experimental testing of each hypothesis. %%% During the development of the embryo organs are formed and shaped from cells. Dr. Hilfer will test the hypothesis that organ formation is controlled primarily by changes in cell shape. He will use microscopic measurements of developing embryos as well as computer models to test this hypothesis.
