A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis

Kumar, N. et al. (2016) A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis. Development, 143(20), pp. 3711-3722. (doi: 10.1242/dev.137992) (PMID:27802136)

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During late gestation, villi extend into the intestinal lumen to dramatically increase the surface area of the intestinal epithelium, preparing the gut for the neonatal diet. Incomplete development of the intestine is the most common gastrointestinal complication in neonates, but the causes are unclear. We provide evidence in mice that Yin Yang 1 (Yy1) is crucial for intestinal villus development. YY1 loss in the developing endoderm had no apparent consequences until late gestation, after which the intestine differentiated poorly and exhibited severely stunted villi. Transcriptome analysis revealed that YY1 is required for mitochondrial gene expression, and ultrastructural analysis confirmed compromised mitochondrial integrity in the mutant intestine. We found increased oxidative phosphorylation gene expression at the onset of villus elongation, suggesting that aerobic respiration might function as a regulator of villus growth. Mitochondrial inhibitors blocked villus growth in a fashion similar to Yy1 loss, thus further linking oxidative phosphorylation with late-gestation intestinal development. Interestingly, we find that necrotizing enterocolitis patients also exhibit decreased expression of oxidative phosphorylation genes. Our study highlights the still unappreciated role of metabolic regulation during organogenesis, and suggests that it might contribute to neonatal gastrointestinal disorders.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Faller, Dr William and Sansom, Professor Owen
Authors: Kumar, N., Srivillibhuthur, M., Joshi, S., Walton, K. D., Zhou, A., Faller, W. J., Perekatt, A. O., Sansom, O. J., Gumucio, D. L., Xing, J., Bonder, E. M., Gao, N., White, E., and Verzi, M. P.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Development
Publisher:Company of Biologists
ISSN (Online):1477-9129
Published Online:18 October 2016
Copyright Holders:Copyright © 2016 Company of Biologists
First Published:First published in Development 143(20):3711-3722
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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