The role of physical forces between epithelia and their external environment in tissue morphogenesis

• Applicant: Professor Dr. Stefan Münster
• Subject Area: Biophysics ; Developmental Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 460111950

Morphogenesis – the biological creation of form in multicellular organisms – requires the coordinated generation of tissue forces. While the gene regulatory networks that control this intricate process have been studied in detail over the last decades, much less is known about the physical mechanisms that drive morphogenetic processes. Since tissues are always in contact with an external environment, forces act not only within the tissue (tissue extrinsic) but also between the tissue and its environment (tissue extrinsic). Although morphogenetic processes must depend on the balance between intrinsic and extrinsic forces, only tissue-intrinsic forces are well studied thus far, whereas tissue-extrinsic forces and their contribution to important morphogenetic processes are not well understood. We propose to study the gastrulation of the red flour beetle (Tribolium castaneum), a process in which a roughly ellipsoidal epithelial tissue folds into a complex three-dimensional shape while being enclosed by a rigid egg shell (and vitelline membrane). We have recently shown that a localized and time-regulated interaction of this tissue with the vitelline membrane leads to considerable tissue-extrinsic forces, which are necessary for normal gastrulation. Building on this discovery, we will now investigate the interaction of these tissue-extrinsic forces with the tissue-extrinsic forces and investigate how tissues can use their environment to create shape. We will use high-resolution light microscopy, image analysis, genetic perturbations, biophysical manipulations, and mathematical modeling of tissue forces and deformations to provide the basis for a better understanding of the basic physical principles of tissue folding in confined spaces. Second, we will investigate whether the beetle epithelium exerts an active (migratory) extrinsic force that might assist the extensive tissue flows during embryonic development. We will develop a new technique to measure the forces between epithelia and their environment directly in the living embryo. Third, we will attempt to recapitulate the identified mechanical components of tissue folding ex vivo using cultured epithelial monolayers. On the one hand, this will allow us to test whether our understanding of the physical principles gained from our study of the beetle epithelium is complete. On the other hand, it will provide the basis for the development of new methodologies for the controlled folding of artificial tissues into three-dimensional structures. Our interdisciplinary work will therefore broaden the basic understanding of the physical principles of morphogenesis and also reveal the principles necessary to create complex architectures in multicellular ex vivo systems, such as organoids.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Konfokalmikroskop mit Inkubationskammer
• Instrumentation Group: 5090 Spezialmikroskope