Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia

Free Radic Biol Med. 2019 Feb 1:131:197-208. doi: 10.1016/j.freeradbiomed.2018.12.006. Epub 2018 Dec 6.


Inadequate delivery of oxygen to organisms during development can lead to cell dysfunction/death and life-long disabilities. Although the susceptibility of developing cells to low oxygen conditions changes with maturation, the cellular and molecular pathways that govern responses to low oxygen are incompletely understood. Here we show that developing Caenorhabditis elegans are substantially more sensitive to anoxia than adult animals and that this sensitivity is controlled by nervous system generated hormones (e.g., neuropeptides). A screen of neuropeptide genes identified and validated nlp-40 and its receptor aex-2 as a key regulator of anoxic survival in developing worms. The survival-promoting action of impaired neuropeptide signaling does not rely on five known stress resistance pathways and is specific to anoxic insult. Together, these data highlight a novel cell non-autonomous pathway that regulates the susceptibility of developing organisms to anoxia.

Keywords: Anoxia; C. elegans; Neuropeptides; egl-3; nlp-40; unc-31.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Hypoxia / genetics*
  • Hypoxia / metabolism
  • Longevity / genetics*
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Oxygen / metabolism
  • Proprotein Convertase 2 / genetics
  • Proprotein Convertase 2 / metabolism
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction


  • Caenorhabditis elegans Proteins
  • Calcium-Binding Proteins
  • NLP-40 protein, C elegans
  • Neuropeptides
  • Receptors, G-Protein-Coupled
  • UNC-31 protein, C elegans
  • aex-2 protein, C elegans
  • EGL-3 proprotein convertase, C elegans
  • Proprotein Convertase 2
  • Oxygen