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Epigenetics in ENS development and Hirschsprung disease

AuthorsTorroglosa, Ana; Alves, M. M.; Fernández, Raquel M.; Antiñolo, Guillermo ; Hofstra, Robert MW; Borrego, Salud
KeywordsNeural crest cells
Hirschsprung disease
Enteric nervous system
Issue Date15-Sep-2016
CitationDevelopmental Biology 417(2): 209-216 (2016)
AbstractHirschsprung disease (HSCR, OMIM 142623) is a neurocristopathy caused by a failure of the enteric nervous system (ENS) progenitors derived from neural crest cells (NCCs), to migrate, proliferate, differentiate or survive to and within the gastrointestinal tract, resulting in aganglionosis in the distal colon. The formation of the ENS is a complex process, which is regulated by a large range of molecules and signalling pathways involving both the NCCs and the intestinal environment. This tightly regulated process needs correct regulation of the expression of ENS specific genes. Alterations in the expression of these genes can have dramatic consequences. Several mechanisms that control the expression of genes have been described, such as DNA modification (epigenetic mechanisms), regulation of transcription (transcription factor, enhancers, repressors and silencers), post-transcriptional regulation (3′UTR and miRNAs) and regulation of translation. In this review, we focus on the epigenetic DNA modifications that have been described so far in the context of the ENS development. Moreover we describe the changes that are found in relation to the onset of HSCR.
Publisher version (URL)http://doi.org/10.1016/j.ydbio.2016.06.017
Identifiersissn: 0012-1606
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