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Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease

Hirschsprung disease (HSCR) is attributed to a failure of neural crest derived cells to migrate, proliferate, differentiate or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. This process requires a wide and complex variety of molecules and signaling pathways whi...

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Autores principales: Enguix-Riego, María Valle, Torroglosa, Ana, Fernández, Raquel María, Moya-Jiménez, María José, de Agustín, Juan Carlos, Antiñolo, Guillermo, Borrego, Salud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754768/
https://www.ncbi.nlm.nih.gov/pubmed/26879676
http://dx.doi.org/10.1038/srep21160
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author Enguix-Riego, María Valle
Torroglosa, Ana
Fernández, Raquel María
Moya-Jiménez, María José
de Agustín, Juan Carlos
Antiñolo, Guillermo
Borrego, Salud
author_facet Enguix-Riego, María Valle
Torroglosa, Ana
Fernández, Raquel María
Moya-Jiménez, María José
de Agustín, Juan Carlos
Antiñolo, Guillermo
Borrego, Salud
author_sort Enguix-Riego, María Valle
collection PubMed
description Hirschsprung disease (HSCR) is attributed to a failure of neural crest derived cells to migrate, proliferate, differentiate or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. This process requires a wide and complex variety of molecules and signaling pathways which are activated by transcription factors. In an effort to better understand the etiology of HSCR, we have designed a study to identify new transcription factors participating in different stages of the colonization process. A differential expression study has been performed on a set of transcription factors using Neurosphere-like bodies from both HSCR and control patients. Differential expression levels were found for CDYL, MEIS1, STAT3 and PAX6. A significantly lower expression level for PAX6 in HSCR patients, would suit with the finding of an over-representation of the larger tandem (AC)m(AG)n repeats within the PAX6 promoter in HSCR patients, with the subsequent loss of protein P300 binding. Alternatively, PAX6 is a target for DNMT3B-dependant methylation, a process already proposed as a mechanism with a role in HSCR. Such decrease in PAX6 expression may influence in the proper function of signaling pathways involved in ENS with the confluence of additional genetic factors to the manifestation of HSCR phenotype.
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spelling pubmed-47547682016-02-24 Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease Enguix-Riego, María Valle Torroglosa, Ana Fernández, Raquel María Moya-Jiménez, María José de Agustín, Juan Carlos Antiñolo, Guillermo Borrego, Salud Sci Rep Article Hirschsprung disease (HSCR) is attributed to a failure of neural crest derived cells to migrate, proliferate, differentiate or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. This process requires a wide and complex variety of molecules and signaling pathways which are activated by transcription factors. In an effort to better understand the etiology of HSCR, we have designed a study to identify new transcription factors participating in different stages of the colonization process. A differential expression study has been performed on a set of transcription factors using Neurosphere-like bodies from both HSCR and control patients. Differential expression levels were found for CDYL, MEIS1, STAT3 and PAX6. A significantly lower expression level for PAX6 in HSCR patients, would suit with the finding of an over-representation of the larger tandem (AC)m(AG)n repeats within the PAX6 promoter in HSCR patients, with the subsequent loss of protein P300 binding. Alternatively, PAX6 is a target for DNMT3B-dependant methylation, a process already proposed as a mechanism with a role in HSCR. Such decrease in PAX6 expression may influence in the proper function of signaling pathways involved in ENS with the confluence of additional genetic factors to the manifestation of HSCR phenotype. Nature Publishing Group 2016-02-16 /pmc/articles/PMC4754768/ /pubmed/26879676 http://dx.doi.org/10.1038/srep21160 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Enguix-Riego, María Valle
Torroglosa, Ana
Fernández, Raquel María
Moya-Jiménez, María José
de Agustín, Juan Carlos
Antiñolo, Guillermo
Borrego, Salud
Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease
title Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease
title_full Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease
title_fullStr Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease
title_full_unstemmed Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease
title_short Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease
title_sort identification of different mechanisms leading to pax6 down-regulation as potential events contributing to the onset of hirschsprung disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754768/
https://www.ncbi.nlm.nih.gov/pubmed/26879676
http://dx.doi.org/10.1038/srep21160
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