Humans exhibit unique cognitive features, including the emergence of complex forms of written and oral communication, our propensity to develop new technologies and our ability to produce artistic representations of our experiences. These unique abilities are ultimately due to developmental changes that increased brain size and circuit complexity during human evolution. The decoding of the human and chimpanzee genomes has provided the means to identify genomic changes that altered human brain development, leading to the evolution of human cognition. However, the functional consequences of such genomic changes remain elusive. This is because, until now, we’ve lacked the conceptual framework and experimental paradigms to decipher the relative contributions of these human-specific genomic changes on the formation and function of the brain.
The Deciphering the Evolutionary Origins of Human Brain Uniqueness project leverages an integrated genetic strategy as well as novel intellectual and technological resources to causally link genetic changes unique to the human genome to the brain features they specify. This strategy consists of several complementary approaches. First, we are using genome editing technologies to introduce human-specific genetic changes into the mouse genome. These “humanized” mouse models will reveal how human-specific genomic features alter brain development, circuitry and function in a living system we can comprehensively study. Second, we are using induced pluripotent stem cells from humans, chimpanzees and other primates to generate and characterize “mini-brains,” three-dimensional cellular structures that mimic the early aspects of brain development. This approach will help us learn how human and chimpanzee brains differ during development and will enable us to identify the genetic changes underlying these divergent developmental outcomes. In conjunction, we are also advancing new technologies that will enable us to study evolutionary changes in the human brain at single-cell resolution. Finally, we will compare the discoveries that emerge from our genetic models with molecular and cellular features of the developing human brain itself. Our findings will provide unprecedented insights into the genetic and cellular mechanisms that influenced the evolution of the human brain, and begin to reveal the events in our evolutionary history that made us human.
This project allies world leaders in genetics, genomics, evolutionary biology and neuroscience. It is jointly led by Franck Polleux, professor of neuroscience in the Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia University, and James P. Noonan, associate professor of genetics, of ecology and evolutionary biology, and of neuroscience at Yale University.
