Programmed cell death eliminates unwanted cells during normal development and physiological homeostasis. While cell interactions can influence apoptosis as they do other types of cell fate, outside of the adaptive immune system little is known about the intercellular cues that actively promote cell death in healthy cells. We used the Caenorhabditis elegans germline as a model to investigate the extrinsic regulators of physiological apoptosis. Using genetic and cell biological methods, we show that somatic gonad sheath cells, which also act as phagocytes of dying germ cells, promote death in the C. elegans germline through VAB-1/Eph receptor signaling. We report that the germline apoptosis function of VAB-1 impacts specific cell death pathways, and may act in parallel to extracellular signal-regulated kinase MAPK signaling. This work defines a non-autonomous, pro-apoptotic signaling for efficient physiological cell death, and highlights the dynamic nature of intercellular communication between dying cells and the phagocytes that remove them.
Bibliographical noteFunding Information:
Acknowledgements. We thank Hongtao Jia for helpful discussions and preliminary experiments, and Steven Billups, Mark Corkins, and Elizabeth Ulm for comments on the manuscript. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR). Work in the Chamberlin lab is supported by the National Science Foundation (NSF).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology