Role of Neuronal differentiation and Regeneration of VHL Tumor Suppressor Gene

点击翻译按钮获取中文摘要

VHL gene and protein are expressed in neuronal cells of fetus and adult brain. However, the role of VHL gene in central nervous system (CNS) has not been elucidated. VHL gene might modify the various gene expressions of during embryogenesis and tumorigenesis in CNS. We investigated the role of 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 central nervous system progenitor cells, and also show that VHL gene transduction induces neuronal differentiation. In addition, a VHLmRNA antisense oligonucleotide inhibits differentiation of CNS progenitor cells and up-regulates their cell cycle. VHL protein can change NSCs into mature functional neuron in the electrophysiological function in vitro and also can differentiate dopamine-secreting neurons in brains of Parkinson model rats. VHL protein plays a critical role for neuronal differentiation of human neuroblastoma cells. Neuroblastoma cells stably expressing VHL protein had neurite-like processes with varicosities, distinct expression of the neuronal markers neuropeptide Y and neurofilament 200, acquired regulated neurosecretion competence in response to depolarizing and cholinergic stimuli, and had large voltage-gated fast sodium currents and delayed rectifier potassium (Kv) currents compatible with mature neurons. In conclusion, VHL gene plays an essential role in neuronal differentiation and VHL-gene induction cells are useful for neuronal regeneration as powerful tool