NSF-ANR: Developmental Mechanics Of Brain Evolution

Harvard University, Cambridge MA

Investigators

Abstract

The geometry of the cerebral cortex is related to its cellular, connective and functional organization. Across species, specific folds are associated with primary sensory and motor functions, as well as with complex functions such as language or creativity. Because of this, brain folding anatomy is widely used in the research of biomarkers for function and dysfunction in such contexts that include psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder. This joint proposal between the PIs focuses on differentiating the role of genetic and mechanical factors influencing the formation of folding patterns across multiple species. The study will use a combination of phylogenetic comparative approaches, reconstructing brain folding trajectories, computational physics and physical gel experiments to understand the development and evolution of the cortex. The trans -Atlantic partnership between two of strongest hubs in the USA and Europe for biological and neuroanatomical research, Paris and Boston, will allow the PIs to synergistically collaborate at the interface between computational neuroscience, physics, neuroimaging, and applied mathematics. Several research groups of biologists and physicists in the Paris/Boston region are interested in the role of mechanical forces during development and evolution, and this project will be a unique opportunity to increase our interactions beyond the confines of this specific project. The analysis of brain folding is currently used in the research for biomarkers of psychiatric disorders, however, little is known about the biological significance of folding variability. All code and data funded by this project will be made available open source, as both PIs have done in the past. Many of the tools work directly in the Web, allowing the PIs to integrate researchers and citizen scientists from all over the world. The project fits within one of NSF's big 10 ideas - understanding the rules of life. Within this question, one of the grandest questions in biology is that of morphogenesis - how do cells and tissue self-organize to create functional organs. This proposal's outcomes will include comparative study of brain cortical morphogenesis across species to understand the origin of folding patterns and the role of mechanical factors in determining them. The use of physical gel experiments and numerical simulations will be of broader interest in understanding other morphogenetic programs in the cerebellum, and other organs besides the brain. By studying different developmental trajectories within and across species, the project will shed light on the link between early, region specific gene expression patterns and the patterns of cortical folding. From an evolutionary standpoint, the project will provide evidence for why there is a strong conservation of folding patterns among phylogenetically related species, such as carnivores or primates. Together, these comparative views will bring about an evolutionary perspective to the study of variability in brain folding, and thus shed light on the link of folding to functionality. This collaborative US/France project is supported by the US National Science Foundation and the French Agence Nationale de la Recherche, where NSF funds the US investigator and ANR funds the partners in France. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.