Notch mediates the glycolytic switch via PI3K/Akt signaling to support embryonic development

Energy metabolism disorder or insufficient energy supply during incubation will affect the development and survival of avian embryos. Especially, β-oxidation could not provide the continuous necessary energy for avian embryonic development due to the increasing energy demand under hypoxic conditions during the mid-late embryonic stages. The role and mechanism of hypoxic glycolysis replacing β-oxidation as the main source of energy supply for avian embryonic development in the mid-late stages is unclear.

Here, we found that in ovo injection with glycolysis inhibitor or γ-secretase inhibitor both decreased the hepatic glycolysis level and impaired goose embryonic development. Intriguingly, the blockade of Notch signaling is also accompanied by the inhibition of PI3K/Akt signaling in the embryonic primary hepatocytes and embryonic liver. Notably, the decreased glycolysis and impaired embryonic growth induced by the blockade of Notch signaling were restored by activation of PI3K/Akt signaling.

Notch signaling regulates a key glycolytic switch in a PI3K/Akt-dependent manner to supply energy for avian embryonic growth. Our study is the first to demonstrate the role of Notch signaling-induced glycolytic switching in embryonic development, and presents new insight into the energy supply patterns in embryogenesis under hypoxic conditions. In addition, it may also provide a natural hypoxia model for developmental biology studies such as immunology, genetics, virology, cancer, etc.