Role of the Cellular Prion Protein in Oligodendrocyte Precursor Cell Proliferation and Differentiation in the Developing and Adult Mouse CNS

Ana Bribián,Franc Llorens,Rosalina Gavín,José Antonio Del Río,Juan María Torres,Manuel Reina,Fernando De Castro,Xavier Fontana,José Manuel García-Verdugo,Shu-Ichi Okamoto

doi:10.1371/journal.pone.0033872

Abstract

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells.

Highlights

Oligodendrocyte maturation and differentiation is a wellorchestrated process that has been studied in detail in isolated oligodendrocyte precursor cells (OPCs) in culture, where the proliferation and differentiation of OPCs is controlled by a welldefined sequence of events
The cell counts in the subgranular zone (SGZ) and granule cell layer of the dentate gyrus revealed that there was 52.9% reduction in the cells that incorporated BrdU cells in Prnp0/0 mice when compared with the Prnp+/+ animals 1 day after the last BrdU pulse
When we investigated the presence of OPCs during perinatal development, we found that Olig2-immunoreactive cells that migrated tangentially from subpalial regions were more abundant (2.5-fold) in the neocortex of Prnp0/0 than in Prnp+/+ embryos (E16.5: Fig. 5A-D,O)

Summary

Introduction

Oligodendrocyte maturation and differentiation is a wellorchestrated process that has been studied in detail in isolated oligodendrocyte precursor cells (OPCs) in culture, where the proliferation and differentiation of OPCs is controlled by a welldefined sequence of events (see for example, [1,2]). The OPCs that persist are considered to be a putative reservoir of mature oligodendrocytes. These cells proliferate and differentiate into myelinating oligodendrocytes in order to maintain myelin in both the healthy and injured brain [9,12,13,14,15,16,17,18,19]. Adult OPCs in the neuronal parenchyma are NG2-positive (see [20] for review) and they are considered to be cycling cells with the capacity to differentiate into mature oligodendrocytes, as well as protoplasmic astrocytes [15] and neurons [13,21]

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Results

Conclusion