REGULATION OF ADHERENS JUNCTION AND MECHANICAL FORCE DURING APOPTOSIS IN EPITHELIAL TISSUE MORPHOGENESIS

Abstract

Apoptosis is known to be important during embryonic development and in the homeostasis maintenance of adult tissues. During apoptosis, the dying cell will be extruded out from the cell plane in an actomyosin ring based manner. The mechanical force generated during apoptosis was demonstrated to exist in dorsal closure during Drosophila embryogenesis, and the force contributes to the development. However, whether the force could help other development processes is unknown. Drosophila abdominal epithelial development during metamorphosis, known as histoblast expansion, is a model system to study tissue dynamics. In this project, I revealed that the apoptosis of larval epidermal cells (LECs) during histoblast expansion could mechanically promote the development. Furthermore, I also investigated how the molecules could spatial-temporally regulate the LEC apoptosis and generate the mechanical force. I revealed that the caspase-3 activity is activated before the force generation during apoptosis. Our results also indicated that in the late stage of apical constriction, the actomyosin ring will separate into two rings upon disengagement of adherens junctions between the apoptotic cell and its neighbors, where the tissue tension is released. In addition, the inner ring forms in the apoptotic cell, and starts to accumulate when the apical constriction starts to enter the fast constricting phase, which generates the intrinsic force to constrict the apoptotic cell. The outer ring forms in the neighbors, and starts to accumulate only when the adherens junction disengages in the late stage of Fast Phase. The outer ring plays the role as extrinsic force to fill in the gap left by apoptotic cell and maintain the tissue integrity, and rebuild the tissue tension to maintain tension homeostasis. Through the whole apical constriction process, the septate junction remains intact and keep the tissue integrity. In conclusion, our results suggested the apoptosis could mechanically contribute to other developmental processes as well, which open an insight into a more universally applied active mechanical role the apoptosis may play. In addition, our results indicated the important role of the intrinsic and extrinsic forces in maintaining the tissue integrity and tissue homeostasis during apoptosis in epithelial tissue morphogenesis.