Exploring the generation and coordination of forces driving morphogenesis

Damian Brunner (Biochemistry, Institute of Molecular Life Sciences, University of Zurich, Switezerland)

Abstract:In the past few years it has become clear that next to genetic programs also forces and tension are fundamental to cell function and the development of organisms. For example, the same stem cells were shown to differentiate into bone-, muscle- or neuronal tissue when cultured on substrates with differing elasticity but otherwise identical growth conditions. We combine classical genetics with real-time fluorescence imaging, electron microscopy and mathematical modeling to study forces contributing to dorsal closure, a wound healing related process taking place in mid-embryogenesis of the fruit fly Drosophila melanogaster. During dorsal closure an eye-shaped, dorsal gap in the epidermis of the embryo is closed. The process begins when the two lateral epidermal cell sheets flanking the opening start converging dorsally. When their leading fronts have sufficiently approached the corresponding cells on both sides recognize each other and fuse. Fusion activity starts at the anterior and posterior corners of the opening from where it moves across the gap similar to closing zippers. The initial tissue convergence involves shape changes of the amnioserosa cells, which fill the opening. This is thought to generate a force pulling the surrounding epidermis dorsally. Closure also involves the formation of a contractile, supra-cellular actin cable that surrounds the opening. By pulling on each other, the zippering epidermis cells generate a third force that is required to push the interjacent amnioserosa cells down inside the embryo. I will present and discuss data integrating descriptive and quantitative analysis with qualitative and mathematical models showing how we tackle the problem of studying forces in the living organism.