The role of von Hippel-Lindau protein in the differentiation of neural progenitor cells under normoxic and anoxic conditions

Von Hippel-Lindau protein (pVHL) normally functions to cause ubiquitin-mediated degradation of hypoxia-inducible factor-1α (HIF-1α) under normoxic but not under hypoxic conditions, and induces neuronal differentiation of neural progenitor cells. However, the role of pVHL in the differentiation of neural progenitor cells under either condition has not been fully elucidated. Herein, we show that under the anoxic condition the expression of pVHL and neuronal markers in neural progenitor cells was inhibited, while HIF-1α was induced. In addition, neural progenitor cells expressing pVHL following gene transfer showed distinct neuronal differentiation and no induction of HIF-1α under the normoxic condition but not under the anoxic condition. In conclusion, neuronal differentiation induced by pVHL is associated with degradation of HIF-1α and occurs normally under the normoxic condition but not under the anoxic condition. Differentiation of neuronal progenitor cells may thus depend on oxygen density.