NSF-ANR: Developmental Mechanics Of Brain Evolution

大脑皮层的几何形状与其细胞、连接和功能组织有关。在不同的物种中，特定的褶皱与主要的感觉和运动功能以及语言或创造力等复杂功能有关。正因为如此，脑折叠解剖学被广泛用于研究功能和功能障碍的生物标志物，包括精神分裂症、双相情感障碍、重度抑郁症和自闭症谱系障碍等精神疾病。这两个pi之间的联合建议侧重于区分影响多物种折叠模式形成的遗传和机械因素的作用。该研究将结合系统发育比较方法，重建大脑折叠轨迹，计算物理学和物理凝胶实验来了解皮层的发育和进化。巴黎和波士顿是美国和欧洲两个最强大的生物和神经解剖学研究中心之间的跨大西洋合作伙伴关系，将使pi能够在计算神经科学，物理学，神经成像和应用数学之间的界面上协同合作。巴黎/波士顿地区的几个生物学家和物理学家研究小组对机械力在发展和进化过程中的作用感兴趣，这个项目将是一个独特的机会，可以在这个特定项目的范围之外增加我们的互动。脑折叠的分析目前被用于精神疾病生物标志物的研究，然而，对折叠变异性的生物学意义知之甚少。该项目资助的所有代码和数据都将开放源代码，就像这两个pi过去所做的那样。许多工具直接在网络上工作，允许pi整合来自世界各地的研究人员和公民科学家。这个项目符合国家科学基金会的十大理念之一——理解生命的规律。在这个问题中，生物学中最重要的问题之一是形态发生——细胞和组织如何自我组织以创造功能器官。该提案的结果将包括跨物种大脑皮层形态发生的比较研究，以了解折叠模式的起源和机械因素在决定它们中的作用。物理凝胶实验和数值模拟的使用将对理解小脑和大脑以外的其他器官的其他形态发生程序产生更广泛的兴趣。通过研究物种内部和物种间不同的发育轨迹，该项目将揭示早期、区域特异性基因表达模式和皮层折叠模式之间的联系。从进化的角度来看，该项目将为为什么在系统发育相关的物种（如食肉动物或灵长类动物）中折叠模式有很强的保守性提供证据。总之，这些比较观点将为研究大脑折叠的可变性带来一个进化的视角，从而阐明折叠与功能的联系。这个美国/法国合作项目由美国国家科学基金会和法国国家研究机构支持，其中美国国家科学基金会资助美国研究者，法国国家研究机构资助法国合作伙伴。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.