Final Report Summary - CORTEXFOLDING (Understanding the development and function of cerebral cortex folding)
The mammalian cerebral cortex expands and folds during embryonic development, and deficits in this process result in severe intellectual impairment, suggesting its importance in the functional organization of cortical circuits and the maximization of brain performance. In this project, we have investigated the cellular and genetic mechanisms controlling the developmental expansion and folding of the cerebral cortex, and evaluated the impact of these processes on its functional performance. To this aim we have used a number of experimental animal models, with a central emphasis placed on the ferret, an experimental animal model that displays cortical folds naturally. We have identified novel and key cellular and genetic mechanisms that regulate the initial formation, and further expansion during embryonic development, of specific germinal layers and progenitor cell types with fundamental roles in cortex size and folding. We have demonstrated that manipulation of such genes that define cortical folding protomaps is sufficient to modify the degree and pattern of cortical folding. Moreover, we have demonstrated that genetic mechanisms promoting enhanced neurogenesis and cortex expansion are highly conserved during vertebrate evolution, from reptiles, and that their modulation during evolution was sufficient for the dramatic expansion in brain size. Finally, we have discovered that cortex size and folding has consequences on the architecture of its functional circuits, but also that this system is highly robust to even major anatomical changes.