The International Journal of Developmental Biology

Int. J. Dev. Biol. 55: 953 - 960 (2011)

Vol 55, Issue 10-11-12

Multiple effects of the cellular prion protein on tooth development

Original Article | Published: 29 September 2011

Yan Zhang1, Seong-Oh Kim1,2, Sibylle Opsahl-Vital1,3, Sunita P. Ho4, Jean-Baptiste Souron3, Charles Kim1, Kurt Giles5,6 and Pamela K. Den Besten*,1

1Department of Orofacial Sciences, University of California San Francisco, USA, 2Department of Pediatric Dentistry, Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Korea, 3University Paris Descartes, EA2496, AP-HP, France, 4Division of Biomaterials and Bioengineering, Department of Preventive and Restorative Dental Sciences, 5Institute for Neurodegenerative Diseases and 6Department of Neurology, University of California San Francisco, USA


The role of the prion protein (PrP) in transmissible spongiform encephalopathies has been the focus of intense investigation. However, less is known about the physiological function of normal cellular PrP (PrPC). In adult human teeth, PrPC has been identified in odontoblasts, cementoblasts and epithelial remnants of Malassez. In this study, we have localized PrPC in developing human and mouse teeth, and investigated the function of PrP using a PrP-knockout (Prnp0/0 ) mouse model. PrPC was detected in developing human and mouse ameloblasts and odontoblasts. In vitro, undifferentiated dental mesenchymal cells from embryonic day 18 (E18) Prnp0/0 mouse molars proliferated much more rapidly compared to age-matched, wild-type (wt) mouse molar dental mesenchymal cells. Histochemistry and immunohistochemical analyses showed a subtle but measurable phenotype, with the absence of PrP resulting in earlier initiation of both dentin and enamel formation. Consistent with this finding, laser microdissected odontoblasts from newborn Prnp0/0 mouse incisors had a reduced proliferation rate, as measured by the expression of proliferating cell nuclear antigen (PCNA), and increased type 1 collagen mRNA expression. Dentin microhardness of the fully erupted molars was reduced and incisal enamel mineralization was delayed in Prnp0/0 compared to age-matched wt mouse teeth. Taken together, these results suggest that PrPC affects multiple processes involved in tooth formation, through regulating the differentiation of ameloblasts and odontoblasts.


tooth development, prion protein, ameloblast, odontoblast

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