Developmental Plasticity of the Cellular Hypoxia Response in Zebrafish, Danio rerio

Abstract

In most organisms the cellular response to hypoxia is mediated by the master regulator hypoxia-inducible factor-1 (HIF-1). Zebrafish embryos can also arrest development (suspended animation) to tolerate low oxygen. I tested the hypothesis that induction of HIF-1 and associated target genes (eg. erythropoietin) during embryonic development would alter the hypoxia tolerance phenotype of larval and adult fish. I exposed zebrafish embryos at 3 developmental stages to acute (4 h) bouts of hypoxia (5% dissolved oxygen, DO) or anoxia (<0.5% DO). I found that embryos that mount a HIF-1 response have a greater hypoxia tolerance as larvae. Additionally, populations that experienced embryonic HIF-1 induction show an increase in the proportion of males (~70% male), that are more hypoxia tolerant than female fish, compared to control populations (~45% male). Overall, induction of HIF-1 during ontogeny alters the larval and adult zebrafish phenotype to better tolerate future hypoxic bouts.