Asymmetric distribution of hypoxia-inducible factor α regulates dorsoventral axis in the early sea urchin embryo

Abstract

Hypoxia signaling is an ancient pathway by which animals can respond to low oxygen. Malfunction of this pathway disturbs the hypoxic acclimation and results in various diseases, including cancers. The role of the hypoxia pathway in early embryogenesis remains unclear. Here, we show that in the sea urchin Strongylocentrotus purpuratus blastula, hypoxia-inducible factor α (HIFα), the downstream transcription factor of this pathway, is localized and transcriptionally active on the future dorsal side. This asymmetric distribution is attributable to its oxygen-sensing ability. Manipulations of the HIFα level entrained the dorsoventral axis, as the side with the higher level of HIFα tends to develop into the dorsal side. Gene expression analyses revealed that HIFα restricted the expression of nodal to the ventral side and activated several genes encoding transcription factors on the dorsal side. We also observed that intrinsic hypoxic signals in the early embryos formed a gradient, which was disrupted under hypoxic conditions. Our results present an unprecedented role of the hypoxia pathway in animal development.