Mammals with large brains and higher cognitive functions have a richly folded cerebral cortex. Folding abnormalities are linked to various cognitive disabilities. Despite its relevance in clinical diagnostics, the causes and consequences of cortex folding remain poorly understood. We propose that cortex folding emerges from a dynamic interplay between mechanical and molecular processes, and that it has major consequences for brain organization and function. This project tests this hypothesis by integrating genomics, cell biology, mechanics of brain development and computational modeling. By using a variety of technologies, animal models and manipulations, our interdisciplinary team will first map molecular, cellular, and mechanical events accompanying cortex folding. Next, we will investigate the effects of genetic perturbations on tissue mechanics, and vice versa, to identify key mechanisms leading to cortex folding and identify their interactions. Then, we will test if these mechanisms are universal by trying to induce folds in species with a smooth brain. Finally, we will decipher the consequences of cortex folding on neural circuit function and animal behavior. Our project integrates current, opposing concepts of cortex folding by adopting an interdisciplinary and multiscale perspective. Results from this project will provide unprecedented insights into the determinants of cortical anatomy and brain organization. Our work, bridging physical and life sciences, will lead to new insights into normal and pathological brain development, paving the way to a new research area of integrated neurobiology with potential applications in modern medicine.
