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BioMed Research International
Volume 2013 (2013), Article ID 182965, 11 pages
http://dx.doi.org/10.1155/2013/182965
Research Article

Expression and Function of NUMB in Odontogenesis

1Department of Orthodontics, College of Dental Medicine, Nova Southeastern University, 3200 S. University Drive, Fort Lauderdale, FL 33328, USA
2Brodie Tooth Development Genetics & Regenerative Medicine Research Laboratory, Department of Oral Biology (M/C 690), College of Dentistry, University of Illinois at Chicago, Chicago IL 60612, USA
3Department of Orthdontics, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago IL 60612, USA

Received 6 January 2013; Revised 2 May 2013; Accepted 13 May 2013

Academic Editor: Avina Paranjpe

Copyright © 2013 Haitao Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

NUMB is a multifunctional protein implicated to function in self-renewal and differentiation of progenitors in several tissues. To characterize the transcripts and to analyze the expression pattern of NUMB in odontogenesis, we isolated 2 full-length clones for NUMB from mouse dental pulp mRNA. One novel sequence contained 200 bp insertion in the phosphotyrosine binding domain (PTB). Confocal microscopy analysis showed strong NUMB expression in human dental pulp stem cells (hDPSC) and preameloblasts. Western blot analysis indicated that NUMB isoforms were differentially expressed in various dental tissues. Immunohistochemical analysis showed that in postnatal mouse tooth germs, NUMB was differentially expressed in the preameloblasts, odontoblasts, cervical loop region, and in the dental pulp stem cells during development. Interestingly, overexpression of NUMB in HAT-7, a preameloblast cell line, had dramatic antagonizing effects on the protein expression level of activated Notch 1. Further analysis of the Notch signaling pathway showed that NUMB significantly downregulates sonic hedgehog (Shh) expression in preameloblasts. Therefore, we propose that NUMB maintains ameloblast progenitor phenotype at the cervical loop by downregulating the activated Notch1 protein and thereby inhibiting the mRNA expression of Shh.