Adult tissues maintain homeostasis with regard to the number of cells in the tissue and the function of differentiated cells. In the case of regenerative tissues, they maintain homeostasis by elimination of malfunctioning cells and compensatory proliferation of proliferative cells such as stem cells. However, non-regenerative tissues do not have the potential to increase the number of cells. Therefore, these tissues need to limit elimination of malfunctioning cells depending on the damage level and keep cells with low damage by proactive resistance to cell death. In this research project, I aim to develop the Drosophila model system to study the homeostasis of non-regenerative tissue and clarify the mechanisms for detection and limited elimination of malfunctioning cells.

To address this research project, I deal with the Drosophila male accessory gland (ACG), an exocrine organ producing seminal fluid. The exocrine cells in ACGs have the following features: 1) cell cycle is arrested in the G0 phase, 2) cell death-resistance is shown, and 3) only aging/malfunctioning cells are eliminated. Thus, the ACG is a suitable model system to study cell death-resistant non-regenerative organs. By using this Drosophila model system, I will examine the signaling pathways that respond to malfunctions of cells and regulate cell death. Moreover, I plan to mimic this specific elimination of cells by manipulation of genetic pathways.

Epithelial tubular tissues face lumen on the apical surface so that the epithelial cells are commonly damaged by outside agents. Thereby, the epithelial tubular tissues carry the risk of producing certain abnormal cells, such as aging-dependent or fatal damage-dependent malfunctioning cells. To avoid the production of malfunctioning cells, tissues detect damaged cells and subsequently eliminate them though simple activation of cell elimination causes the regression of tissue, especially for non-regenerative or low-proliferative tissues. Therefore, it is important to detect the damage levels of cells and eliminate only highly damaged cells. However, these mechanisms to eliminate abnormal cells depending on the damage level are enigmatic. The development of the Drosophila model system contributes to understanding these mechanisms of maintenance of tissue homeostasis. Moreover, the clarification of the concept of the genetic network to regulate them is expected to clue the understanding of many age-related human diseases.