“Too much guts and not enough brains”: (epi)genetic mechanisms and future therapies of Hirschsprung disease — a review

Clinical Epigenetics

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[1] 0000 0004 0389 8485, grid.55325.34, Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, 0027, Oslo, Norway;0000 0004 0389 7802, grid.459157.b, Department of Surgery, Baerum Hospital, Vestre Viken Hospital Trust, 3004, Drammen, Norway;0000 0004 0389 8485, grid.55325.34, Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, 0027, Oslo, Norway;0000 0004 0389 8485, grid.55325.34, Department of Pediatric Surgery, Oslo University Hospital, Rikshospitalet, 0424, Oslo, Norway;0000 0004 1936 8921, grid.5510.1, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317, Oslo, Norway;0000 0004 0389 8485, grid.55325.34, Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, 0027, Oslo, Norway;0000 0004 1936 8921, grid.5510.1, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317, Oslo, Norway;0000 0004 0389 8485, grid.55325.34, Department of Pediatric Surgery, Oslo University Hospital, Rikshospitalet, 0424, Oslo, Norway;0000 0004 1936 8921, grid.5510.1, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0317, Oslo, Norway;000000041936754X, grid.38142.3c, Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;

关键词: Enteric nervous system;    Epigenetics;    Development;    HSCR;    Hirschsprung;    Neural crest;    Cell therapy;   

DOI  :  10.1186/s13148-019-0718-x

来源: publisher

【 摘 要 】

Hirschsprung disease is a neurocristopathy, characterized by aganglionosis in the distal bowel. It is caused by failure of the enteric nervous system progenitors to migrate, proliferate, and differentiate in the gut. Development of an enteric nervous system is a tightly regulated process. Both the neural crest cells and the surrounding environment are regulated by different genes, signaling pathways, and morphogens. For this process to be successful, the timing of gene expression is crucial. Hence, alterations in expression of genes specific for the enteric nervous system may contribute to the pathogenesis of Hirschsprung’s disease. Several epigenetic mechanisms contribute to regulate gene expression, such as modifications of DNA and RNA, histone modifications, and microRNAs. Here, we review the current knowledge of epigenetic and epitranscriptomic regulation in the development of the enteric nervous system and its potential significance for the pathogenesis of Hirschsprung’s disease. We also discuss possible future therapies and how targeting epigenetic and epitranscriptomic mechanisms may open new avenues for novel treatment.

【 授权许可】

CC BY