Prion protein and neuronal differentiation: quantitative analysis of prnp gene expression in a murine inducible neuroectodermal progenitor

The biological function of the cellular prion protein, PrPc, is currently u nknown. The presence of PrPc transcripts in the developing neural tube from embryonic day 13.5 and the predominant expression of PrPc in the adult bra in is suggestive of a role in the onset and/or modulation of neuronal funct ions, We took advantage of the bipotential neuroectodermal 1C11 cell line t o monitor PrPc expression during its bioaminergic differentiations. The F9- derived 1C11 precursor cell line displays a stable and immature phenotype i n the absence of extracellular signal and, upon induction, has the capacity to acquire a complete serotonergic or noradrenergic phenotype, the two pat hways being mutually exclusive. A real-time quantitative PCR assay was deve loped to assess PrPc gene expression at: definite rimes of the two programs that correspond to sequential acquisition of neurotransmitter-specific fun ctions. 1C11 cells and their differentiated progenies express significant a mounts of PrP transcripts and of the corresponding protein. A unique decrea se in prnp gene expression is observed upon entry into the serotonergic pat hway, correlating with a downregulation at the protein level. Moreover, ner ve growth factor (NGF) is shown to induce a decrease in the level of prnp g ene expression along the serotonergic - but nor: the noradrenergic - pathwa y. Our study accurately establishes that prnp gene expression (i) is strong ly upregulated concomitantly with cell fate restriction of multipotential c ells towards the neural lineage; (ii) is differentially regulated along the serotonergic versus noradrenergic differentiation program of a unique neur oectodermal progenitor. The 1C11 cell line may provide a new tool for study ing prion infectivity in a well-defined neuronal context. (C) 1999 Editions scientifiques et medicales Elsevier SAS.