Fully wired
The enteric nervous system (ENS), the “little brain” that resides within the gut wall, governs motility, secretion, and blood flow in the human gastrointestinal tract. Failure of the ENS to develop normally leads to congenital megacolon (Hirschsprung Disease) while loss of normal gut innervation is thought to contribute to debilitating motility disorders, such as irritable bowel syndrome. In order to prevent and treat these conditions, it is necessary to understand the molecular mechanisms that control the formation and function of the ENS. Vassilis Pachnis and colleagues found that the planar cell polarity (PCP) genes, Celsr3 and Fzd3 are required for the formation of the complex neural networks within the guts of mice. Inactivation of these genes resulted in disorganization of neuronal projections, slower gut transit time and abnormal colonic motility, indicating for the first time that improper ENS wiring contributes to gastrointestinal motility disorders. You can watch videos of colonic peristalsis in wild type and mutant animals. Here, they used fluorescent labeling to track enteric neurite outgrowth in wild type and PCP-deficient mouse embryos. Future studies will be required to determine if mutations or dysfunction of these genes contributes to human gut motility disorders.
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Citation Information: J Clin Invest. 2013;123(4):1763-1772. https://doi.org/10.1172/JCI66759.
Abstract
A highly complex network of intrinsic enteric neurons is required for the digestive and homeostatic functions of the gut. Nevertheless, the genetic and molecular mechanisms that regulate their assembly into functional neuronal circuits are currently unknown. Here we report that the planar cell polarity (PCP) genes
Authors
Valentina Sasselli, Werend Boesmans, Pieter Vanden Berghe, Fadel Tissir, André M. Goffinet, Vassilis Pachnis
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ISSN: 0021-9738 (print), 1558-8238 (online)