期刊
STEM CELLS
卷 32, 期 6, 页码 1674-1687出版社
WILEY
DOI: 10.1002/stem.1663
关键词
Proliferation; Neurogenesis; Neuroblasts; Neurosphere culture; Subventricular zone
资金
- E.U. FP7 REGPOT Project [264083 NEUROSIGN]
- Hellenic General Secretariat for Research and Technology Grant SYNERGASIA-NOISEPLUS [09SYN-21-969]
- Foundation BNP Paribas
- National Scholarships Foundation (IKY)
- framework action KRIPIS to the Hellenic Pasteur Institute: Development proposals of Research Institutions - European Regional Development Fund and national resources
Cellular prion protein (PrP) is prominently expressed in brain, in differentiated neurons but also in neural stem/precursor cells (NPCs). The misfolding of PrP is a central event in prion diseases, yet the physiological function of PrP is insufficiently understood. Although PrP has been reported to associate with the neural cell adhesion molecule (NCAM), the consequences of concerted PrP-NCAM action in NPC physiology are unknown. Here, we generated NPCs from the subventricular zone (SVZ) of postnatal day 5 wild-type and PrP null (-/-) mice and observed that PrP is essential for proper NPC proliferation and neuronal differentiation. Moreover, we found that PrP is required for the NPC response to NCAM-induced neuronal differentiation. In the absence of PrP, NCAM not only fails to promote neuronal differentiation but also induces an accumulation of doublecortin-positive neuronal progenitors at the proliferation stage. In agreement, we noted an increase in cycling neuronal progenitors in the SVZ of PrP-/- mice compared with PrP+/+ mice, as evidenced by double labeling for the proliferation marker Ki67 and doublecortin as well as by 5-bromo-20-deoxyuridine incorporation experiments. Additionally, fewer newly born neurons were detected in the rostral migratory stream of PrP-/- mice. Analysis of the migration of SVZ cells in microexplant cultures from wild-type and PrP-/- mice revealed no differences between genotypes or a role for NCAM in this process. Our data demonstrate that PrP plays a critical role in neuronal differentiation of NPCs and suggest that this function is, at least in part, NCAM-dependent.
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