RT Journal Article
T1 Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease.
A1 Enguix-Riego, Maria Valle
A1 Torroglosa, Ana
A1 Fernandez, Raquel Maria
A1 Moya-Jimenez, Maria Jose
A1 de-Agustin, Juan Carlos
A1 Antiñolo, Guillermo
A1 Borrego, Salud
K1 Gene expression
K1 Medical genetics
AB 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.
PB Nature Publishing Group
YR 2016
FD 2016-02-16
LK http://hdl.handle.net/10668/9838
UL http://hdl.handle.net/10668/9838
LA en
NO Enguix-Riego MV, Torroglosa A, Fernández RM, Moya-Jiménez MJ, de Agustín JC, Antiñolo G, et al.. Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease. Sci Rep. 2016 Feb 16;6:21160.
NO This work was supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, Spain (PI1301560) and Regional Ministry of Innovation, Science and Enterprise of the Autonomous Government of Andalucia (CTS-7447). MVE-R is supported by fellowship PI11/00533 from ISCIII. We would like to thank all the patients that participated in this study.
DS RISalud
RD Jun 1, 2025