Epigenetic Mechanisms in Hirschsprung Disease

Abstract

Hirschsprung disease (HSCR, OMIM 142623) is due to a failure of enteric precursor cells derived from neural crest (EPCs) to proliferate, migrate, survive or differentiate during Enteric Nervous System (ENS) formation. This is a complex process which requires a strict regulation that results in an ENS specific gene expression pattern. Alterations at this level lead to the onset of neurocristopathies such as HSCR. Gene expression is regulated by different mechanisms, such as DNA modifications (at the epigenetic level), transcriptional mechanisms (transcription factors, silencers, enhancers and repressors), postranscriptional mechanisms (3'UTR and ncRNA) and regulation of translation. All these mechanisms are finally implicated in cell signaling to determine the migration, proliferation, differentiation and survival processes for correct ENS development. In this review, we have performed an overview on the role of epigenetic mechanisms at transcriptional and posttranscriptional levels on these cellular events in neural crest cells (NCCs), ENS development, as well as in HSCR.

Keywords: Hirschsprung disease; enteric nervous system development; epigenetic mechanisms; neural crest cells.

Figure 1

Scheme of the epigenetic processes implicated in Neural Crest Cells (NCCs) and Enteric Nervous System (ENS) development in HSCR context. Epigenetic mechanisms identified in NCC development (A) and in ENS formation (B) with a possible role in the onset of the disease. Adapted from http://www.columbia.edu/itc/hs/medical/humandev/2006/HD10/ENS6.pdf.