This proposal addresses a fundamental question of biology: how did complex organisms arise? A hallmark of complex organisms is that they are composed of a larger number different cell types than simpler organisms. Complex organisms are the most spectacular manifestation of the creativity of the natural world, yet our understanding of this process is very limited. This is largely a result of a lack of conceptual clarity as well as previous limitations to experimental techniques. This project will be based on important conceptual advances by the PI as well as take advantage of recent advances in functional genomic technologies.
To understand how complex organisms evolved from simpler ones, we will investigate the mechanisms that led to the origin of a novel cell type in mammals, i.e. the decidual cell. This cell type is part of the uterus lining (the endometrium) that contributes to the placenta. It is found in placental mammals but not in marsupials (opossums and kangaroos) or more distantly related animals. Specifically, we will combine cutting edge genomic technology to determine the evolution of gene regulation in these cells. By comparing decidual cells from placental mammals to endometrial cells from marsupials, we will characterize for the first time the key gene regulatory features that played an active role in the evolution and origin of new cell types. Concrete outputs include numerous publications in leading scientific journals and presentations at academic conferences. Additionally, to connect the ideas to the broader scientific community, we propose to organize a symposium on cell type evolution. This project stands to substantially advance our understanding of evolution and biological complexity by providing a mechanistic model of how organismal complexity comes into being. The work will contribute significantly to fields other than evolutionary biology, including philosophy of biology as well as developmental and cellular biology.