Uwe Toepfer

The formation of tissues and organs into their final shape requires dynamic interactions between the extracellular matrix (ECM) and their underlying cells. ECM mechanical properties provide mechanical force that is sensed by the cells and transduced into signals resulting in adaptive intracellular changes. However, little is known about how ECM mechanical heterogeneity is locally induced in a developing organ and how these differences affect cellular dynamics and morphogenesis. An excellent model system to study how heterogeneity of the ECM is established and how this leads to the shape of a tissue or organ is the Drosophila egg chamber. Egg chambers are initially round and then elongate along their anterior-posterior axis. During this process, an ECM mechanical heterogeneity with a lower stiffness at the termini and higher stiffness at the centre has to be established for shaping the tissue. How this mechanical gradient is built up and how differential mechanical properties of the ECM alter mechanosensitive cellular behaviour is largely unknown. To address this question, I will characterize a prospective role of Adam-TS proteases for local ECM remodelling to couple this data with direct biophysical measurements of ECM mechanical properties. Second, I will address the question of how differential ECM mechanical properties stimulate cell behaviour to allow egg chamber elongation. Here I want to study the link of ECM mechanics and patterning along the AP axis. In order to understand how local differential ECM mechanical properties are established and how they lead to differential cell behaviour, I will study mechanotransduction and mechanosensitive cell junctional modelling and their dependency on AdamTS protease regulated ECM remodelling. This project should raise insights into the process of local ECM remodelling and the requirement of a heterogeneous ECM to form tissues and organs.