Role of the von Hippel-Lindau tumor suppressor protein during neuronal differentiation.

The von Hippel-Lindau (VHL) tumor suppressor protein down-regulates transcription by transcriptional elongation enhanced by antagonizing elongin B and C. Transcriptional regulation is an important control mechanism for embryogenesis and tumorigenesis. The VHL gene and protein are expressed in neuronal cells of the fetal and adult brain. However, the role of the VHL gene in the central nervous system (CNS) has not been elucidated. The VHL gene might modify the expression of various genes during embryogenesis and tumorigenesis in CNS. We investigated the role of the VHL gene in CNS development using rodent CNS progenitor cells. Here we show that expression of the VHL protein is correlated with neuronal differentiation but not with glial differentiation in CNS progenitor cells, and we also show that VHL gene transduction induces neuronal differentiation. In addition, a VHL mRNA antisense oligonucleotide inhibits differentiation of CNS progenitor cells and up-regulates their cell cycle. In conclusion, the VHL gene plays an essential role in neuronal differentiation as well as transcription.