Deciphering the role of mechanics for epithelia trans-differentiation

• Applicant: Dr. Alba Diz-Muñoz
• Subject Area: Biophysics ; Developmental Biology ; Cell Biology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 414058537

In the last decade it has become clear that cellular and microenvironment mechanics affect epithelia integrity and cell fate. Upon mechanical injury of the zebrafish notochord, cell fate plasticity occurs as epithelial sheath cells trans-differentiatiate into non-epithelial vacuolated ones. For sheath tissue integrity, such trans-differentiation requires the coordination of the cell’s cytoskeleton with a concomitant rearrangement of their cell-cell junctions. A clear understanding of the molecular and physical mechanisms governing cell trans-differentiation in vivo have been hampered by the lack of convenient assay systems and tools to assess and perturb mechanical properties in 3D environments. In this proposal, we will first characterize cell-cell junctions in sheath cells by light and electron microscopy, while quantifying tissue stiffness by Brillouin microscopy upon controlled vacuolated cell death (Objective 1). Next, we will perturb the balance of forces between neighbouring sheath cells by developing strategies to systematically change tissue stiffness, neighbouring cell contractility and adhesion, while assessing their effect on fate and cell-cell junctions’ dynamics during epithelia trans-differentiation (Objective 2).

• DFG Programme: Priority Programmes
• Subproject of: SPP 1782: Epithelial intercellular junctions as dynamic hubs to integrate forces, signals and cell behaviour