Physical aspects of Drosophila Gastrulation

The proper function of organisms, their organs, and their tissues requires them to have specific shape. How this shape is specified and maintained is a fundamental question in biology. In animals, the shape is determined through the process of morphogenesis, a concerted sequence of tissue remodeling events leading up to the final body plan. Despite a long-standing effort to understand the physical mechanisms that underlie morphogenesis, these mechanisms still remain largely unknown. Basic considerations from physics imply that in order to completely determine the mechanism of a morphogenetic change, two pieces of information are absolutely required: (1) material/mechanical properties of the tissue, and (2) the active forces that drive tissue deformation. Using Drosophila gastrulation as a model, and by combining biophysical, molecular, and modeling methods, we propose an approach sufficient to determine both. Recent work from our group and others has begun the process of quantifying the mechanical properties of tissues as whole. However, it has become clear that mechanical properties vary in different cellular regions (apical vs basal etc.), and that understanding these differences is crucial for correctly understanding and accurately predicting morphogenesis. In Aim 1, we expand upon our previously established techniques for measuring tissue mechanics, and apply them to directly measure viscous and elastic properties of the apical, lateral, and basal cellular compartments separately. In Aim 2, we will incorporate these measurements into a comprehensive computational model to explain large-scale tissue behaviors based on these microscopic measurements. From this model, we will also be able to extract the spatial and temporal force profiles driving tissue morphogenesis in the early embryo. In Aim 3 we will assess the predictive power of our model to predict mutant phenotypes, and we will also begin identifying the molecular players that contribute to specific mechanical features such as elasticity and mechanical memory. In summary, successful completion of the project will for the first time establish a comprehensive biophysical mechanism of a key model system. Both the techniques and general approach developed here will be applicable to a wide variety of tissue morphogenesis processes.