Hypoxia-inducible factor-1 mediates adaptive developmental plasticity of hypoxia tolerance in zebrafish, Danio rerio

Proc Biol Sci. 2014 Jul 7;281(1786):20140637. doi: 10.1098/rspb.2014.0637.


In recent years, natural and anthropogenic factors have increased aquatic hypoxia the world over. In most organisms, the cellular response to hypoxia is mediated by the master regulator hypoxia-inducible factor-1 (HIF-1). HIF-1 also plays a critical role in the normal development of the cardiovascular system of vertebrates. We tested the hypothesis that hypoxia exposures which resulted in HIF-1 induction during embryogenesis would be associated with enhanced hypoxia tolerance in subsequent developmental stages. We exposed zebrafish (Danio rerio) embryos to just 4 h of severe hypoxia or total anoxia at 18, 24 and 36 h post-fertilization (hpf). Of these, exposure to hypoxia at 24 and 36 hpf as well as anoxia at 36 hpf activated the HIF-1 cellular pathway. Zebrafish embryos that acutely upregulated the HIF-1 pathway had an increased hypoxia tolerance as larvae. The critical window for hypoxia sensitivity and HIF-1 signalling was 24 hpf. Adult male fish had a lower critical oxygen tension (Pcrit) compared with females. Early induction of HIF-1 correlated directly with an increased proportion of males in the population. We conclude that mounting a HIF-1 response during embryogenesis is associated with long-term impacts on the phenotype of later stages which could influence both individual hypoxia tolerance and population dynamics.

Keywords: Hypoxia-inducible factor-1 cellular pathway; developmental plasticity; hypoxia tolerance; sex ratio bias; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaerobiosis*
  • Animals
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / physiology
  • Female
  • Hypoxia-Inducible Factor 1 / genetics*
  • Hypoxia-Inducible Factor 1 / metabolism
  • Larva / genetics
  • Larva / growth & development
  • Larva / physiology
  • Male
  • Oxygen / metabolism*
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / growth & development
  • Zebrafish / physiology*


  • Hypoxia-Inducible Factor 1
  • Oxygen