Autophagy genes function in apoptotic cell corpse clearance during C. elegans embryonic development

Abstract

Efficient apoptotic corpse clearance is essential for metazoan development and adult tissue homeostasis. Several autophagy proteins have been previously shown to function in apoptotic cell clearance; however, it remains unknown whether autophagy genes are essential for efficient apoptotic corpse clearance in the developing embryo. Here we show that, in Caenorhabditis elegans embryos, loss-of-function mutations in several autophagy genes that act at distinct steps in the autophagy pathway resulted in increased numbers of cell corpses and delayed cell corpse clearance. Further analysis of embryos with a null mutation in bec-1, the C. elegans ortholog of yeast VPS30/ATG6/mammalian beclin 1 (BECN1), revealed normal phosphatidylserine exposure on dying cells. Moreover, the corpse clearance defects of bec-1(ok691) embryos were rescued by BEC-1 expression in engulfing cells, and bec-1(ok691) enhanced corpse clearance defects in nematodes with simultaneous mutations in the engulfment genes, ced-1, ced-6 or ced-12. Together, these data demonstrate that autophagy proteins play an important role in cell corpse clearance during nematode embryonic development, and likely function in parallel to known pathways involved in corpse removal.

Keywords: :

• autophagy
• apoptotic corpse clearance
• C. elegans
• embryogenesis
• cell death

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors thank Dr. Hong Zhang, Dr. Michael O. Hengartner, and Dr. Bruce Bamber for providing nematode strains and reagents, and Dr. Katherine Luby-Phelps and Mr. Abhijit Bugde in the UTSW Live Cell Imaging Core for assistance with microscopy. 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). The work in the authors’ laboratory was funded by NIH awards RO1 CA109618 (B.L.) and GM067848 (Z.Z.); and an Ellison Medical Foundation New Scholars Award in Aging (K.J.)