Establishment of Extracellular matrix mechanical heterogeneity by AdamTS proteases in the Drosophila egg chamber

• Applicant: Dr. Uwe Töpfer
• Subject Area: Developmental Biology ; General Genetics and Functional Genome Biology ; Biophysics ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 512432663

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 center 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 behavior is largely unknown. To address this question, this project has two aims. In part 1 I will characterize a prospective role of Adam-TS proteases for local ECM remodeling to couple this data with direct biophysical measurements of ECM mechanical properties. Hereby, it is still unclear through which structural parameters and which material abilities are affecting morphogenesis and how they are interconnected. This comparative data will provide a comprehensive overview of structural and mechanical changes and raise fundamental insights about the role of the ECM for morphogenesis. In part 2 I will address the question of how differential ECM mechanical properties stimulate cell behavior 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 behavior, I will study mechanotransduction and mechanosensitive cell junctional modeling and their dependency on AdamTS protease regulated ECM remodeling. This project should raise insights into the process of local ECM remodeling and the requirement of a heterogeneous ECM to form tissues and organs.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professor Dr. Guy Tanentzapf