University of Illinois Chicago
Browse

Expression and Function of NUMB in Odontogenesis

Download (15.59 MB)
journal contribution
posted on 2015-09-21, 00:00 authored by Haitao Li, Amsaveni Ramachandran, Qi Gao, Sriram Ravindran, Yiqiang Song, Carla Evans, Anne George
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.

Funding

This work is supported by NIH Grant DE 11657, Brodie Endowment Fund, research funding provided by Department of Orthodontics, University of Illinois at Chicago, and the American Association of Orthodontists Foundation (AAOF).

History

Publisher Statement

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. This is a copy of an article published in the BioMed Research International © 2013 Hindawi Publishing Corporation

Publisher

Hindawi Publishing Corporation

Language

  • en_US

issn

2314-6133

Issue date

2013-01-01

Usage metrics

    Categories

    No categories selected

    Keywords

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC