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Expression and Function of NUMB in Odontogenesis

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 n...

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Autores principales: Li, Haitao, Ramachandran, Amsaveni, Gao, Qi, Ravindran, Sriram, Song, Yiqiang, Evans, Carla, George, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690219/
https://www.ncbi.nlm.nih.gov/pubmed/23841055
http://dx.doi.org/10.1155/2013/182965
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author Li, Haitao
Ramachandran, Amsaveni
Gao, Qi
Ravindran, Sriram
Song, Yiqiang
Evans, Carla
George, Anne
author_facet Li, Haitao
Ramachandran, Amsaveni
Gao, Qi
Ravindran, Sriram
Song, Yiqiang
Evans, Carla
George, Anne
author_sort Li, Haitao
collection PubMed
description 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.
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spelling pubmed-36902192013-07-09 Expression and Function of NUMB in Odontogenesis Li, Haitao Ramachandran, Amsaveni Gao, Qi Ravindran, Sriram Song, Yiqiang Evans, Carla George, Anne Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2013 2013-06-06 /pmc/articles/PMC3690219/ /pubmed/23841055 http://dx.doi.org/10.1155/2013/182965 Text en Copyright © 2013 Haitao Li et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Li, Haitao
Ramachandran, Amsaveni
Gao, Qi
Ravindran, Sriram
Song, Yiqiang
Evans, Carla
George, Anne
Expression and Function of NUMB in Odontogenesis
title Expression and Function of NUMB in Odontogenesis
title_full Expression and Function of NUMB in Odontogenesis
title_fullStr Expression and Function of NUMB in Odontogenesis
title_full_unstemmed Expression and Function of NUMB in Odontogenesis
title_short Expression and Function of NUMB in Odontogenesis
title_sort expression and function of numb in odontogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690219/
https://www.ncbi.nlm.nih.gov/pubmed/23841055
http://dx.doi.org/10.1155/2013/182965
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