Search for the missing lncs: gene regulatory networks in neural crest development and long non-coding RNA biomarkers of Hirschsprung's disease

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Abstract

Hirschsprung's disease (HSCR), a birth defect characterized by variable aganglionosis of the gut, affects about 1 in 5000 births and is a consequence of abnormal development of neural crest cells, from which enteric ganglia derive. In the companion article in this issue (Shen et al., Neurogasterenterol Motil 28: 266–73), the authors search for long non-coding RNAs (lncRNAs) differentially expressed in bowel tissues of infants with HSCR. Microarray analysis of over 37 000 lncRNAs and 34 000 mRNAs was done. The key result was identification of a set of 5 lncRNAs that is a potential diagnostic biomarker of HSCR. In this minireview, I provide an overview of neural crest development and the gene regulatory networks involved in specification, epithelial–mesenchymal transition, and migration of neural crest cells. Genes involved in later development, proliferation, and differentiation of neural crest cells as they migrate into the gut are also reviewed. Many of these genes are associated with HSCR, including RET, GDNF, GFRα, EDN3, and EDNRB. LncRNAs and their roles in development and disease and their use as biomarkers are discussed. The authors of the companion article previously used a multipronged approach to elucidate the etiology of HSCR by examining the effects of specific miRNAs or lncRNAs and target genes on cell migration, proliferation, cell cycle, and apoptosis in vitro. These studies are discussed in terms of their elegance and limitations. The companion article identifies many new lncRNAs that, in addition to providing potential biomarkers of HSCR, may be a treasure trove for future investigations.

This is a minireview based on a featured article in the same issue. The minireview covers neural crest cell development, particularly gene regulatory networks, and its role in the development of the enteric nervous system. Roles of non-coding RNAs are discussed, with focus on long non-coding RNAs. The contributions made by the featured article are discussed.

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