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.Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad PI1301560Consejería de Innovación, Ciencia y Empresa CTS-744
