Cell fate to mechanical cellular properties: coordinated cell behaviours during Drosophila gastrulation

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During the development of an organism, cells change their shapes in many ways to contribute to the creation of tissues and organs. A common way of creating complex shapes in animals is the folding of two-dimensional, flat epithelia into three-dimensional higher order structures. A particularly well studied example for this is the formation of the ‘ventral furrow’, the first morphogenetic event during the early development of the Drosophila embryo. We know the genes and the mechanisms that trigger a contraction of the cells that form the furrow, which results to an indentation in the epithelium. Much less is known about how cells outside the furrow participate in the process, and thereby enable it. We have discovered differences in the mechanical properties of different cell populations in the embryo, and found that these differences matter for the proper formation of the furrow. But we do not understand the molecular or biochemical basis. The aim of this project is to discover it.The mechanical properties of the cells in the embryo are determined by the proteins in each cell. For many proteins it is not only the presence or absence (or precise level) that may matter, but also their state of activity, which is in turn controlled by other proteins. If two hypothetical cells that are identical in all respects apart from their mechanical properties, they should differ only, or at least mainly, in those protein activities that govern mechanical properties. This is the assumption on which our proposal is based, and it is these proteins that we aim to identify. The early Drosophila embryo is an ideal system for this because up to the period of gastrulation, the 6000 cells of the embryo contain more or less identical sets of proteins. We will find the proteins that are of interest to us by determining the entire set of proteins in each of three cell populations along the dorso-ventral axis that represent the populations participating in furrow formation. We will then compare these sets, as well as markers for the state of activity of the proteins in each set. Not all of the proteins we may find that differ between the populations will necessarily be directly involved in cell mechanics. We will select proteins for detailed study based on further assumptions, for example that components of the cytoskeleton and cell adhesion complexes play the most important roles in determining mechanical cell properties. Classic and novel genetic methods will then be used to manipulate these proteins in the embryo, and assess they outcomes of these manipulations, as a means of testing our hypotheses.