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

Autophagy. 2013 Feb 1;9(2):138-49. doi: 10.4161/auto.22352. Epub 2012 Oct 29.

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: C. elegans; apoptotic corpse clearance; autophagy; cell death; embryogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Autophagy / genetics*
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Count
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development / genetics*
  • Genes, Helminth / genetics
  • Mutation / genetics
  • Phagocytosis / genetics
  • Phosphatidylserines / metabolism
  • Promoter Regions, Genetic / genetics

Substances

  • Caenorhabditis elegans Proteins
  • Phosphatidylserines