Tissue Homeostasis through Cell Competition and Compensation

Tulane University, New Orleans LA

Investigators

Abstract

This project will study a basic question in cell and developmental biology, a novel mechanism by which cells maintain tissues in a healthy state. Healthy cells monitor their neighbors and induce sick cells to undergo cell death, followed by compensating growth and division of the healthy cells, so that the tissue keeps the same number of cells and all the cells are healthy. These studies will provide new insight into how the fine control of this process occurs to repair damaged tissues, and how it changes in aging tissues. In addition to its scientific merit, the project will also integrate research and science education. The knowledge obtained will be used as data for classroom presentation to stimulate students' interest in scientific research. Furthermore, the PI will recruit high-school and undergraduate students from underrepresented groups to participate in the project. Students will carry out directed independent research in the areas of molecular biology and genetics, and learn not only the basic technology but also critical scientific thinking, which will benefit their future careers. The PI will also present in local schools and will bring the project-related research to an undergraduate experimental course. These activities will promote the participation of underrepresented groups and have a broad impact on society at large. In their recent studies, the PI and colleagues found that, in post-mitotic Drosophila follicular epithelia, normal cells play an active role in eliminating aberrant but viable neighbors through JNK-dependent "cell competition," and undergo sporadic cellular hypertrophy to repair the tissue. This "compensatory cellular hypertrophy" (CCH) is probably a general cellular mechanism for post-mitotic tissue homeostasis, as it is also induced when some cells in the post-mitotic follicular epithelium fail to grow to their full size. The PI and colleagues further found that CCH is induced by hyperactivation of insulin- or IGF (insulin-like growth factor)-like signaling (IIS) in hypertrophic cells. In the proposed study, they will determine the mechanisms underlying post-mitotic cell competition and CCH processes. This research will address the following specific aims: (1) To reveal the mechanisms underlying loser cell elimination in post-mitotic cell competition. Under this aim, crucial questions such as how JNK signaling is activated in winner cells neighboring loser cells, and how this pathway executes its effect to eliminate loser cells via apoptosis, will be addressed. (2) To determine the mechanisms by which loss of local tissue volume induces CCH. This aim focuses on how changes in local tissue volume are translated into IIS signaling activation in certain winner cells, and how cellular hypertrophy is regulated. They will test the hypothesis that homeostatic CCH is induced by tensile forces caused by loss of local tissue volume.