Planar cell polarity genes control the connectivity of enteric neurons
Valentina Sasselli, … , André M. Goffinet, Vassilis Pachnis
Valentina Sasselli, … , André M. Goffinet, Vassilis Pachnis
Published March 8, 2013
Citation Information: J Clin Invest. 2013;123(4):1763-1772. https://doi.org/10.1172/JCI66759.
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Planar cell polarity genes control the connectivity of enteric neurons

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 Celsr3 and Fzd3 are required during murine embryogenesis to specifically control the guidance and growth of enteric neuronal projections relative to the longitudinal and radial gut axes. Ablation of these genes disrupts the normal organization of nascent neuronal projections, leading to subtle changes of axonal tract configuration in the mature enteric nervous system (ENS), but profound abnormalities in gastrointestinal motility. Our data argue that PCP-dependent modules of connectivity established at early stages of enteric neurogenesis control gastrointestinal function in adult animals and provide the first evidence that developmental deficits in ENS wiring may contribute to the pathogenesis of idiopathic bowel disorders.

Authors

Valentina Sasselli, Werend Boesmans, Pieter Vanden Berghe, Fadel Tissir, André M. Goffinet, Vassilis Pachnis

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Figure 1

Celsr3 and Fzd3 are expressed in the developing ENS.

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Celsr3 and Fzd3 are expressed in the developing ENS. In situ hybridiz...
In situ hybridization histochemistry on serial transverse sections of E12.5 (A–C), E14.5 (D–F), and E16.5 (G–I) wild-type embryos using riboprobes specific for Ret (A, D, and G), Celsr3 (B, E, and H), and Fzd3 (C, F, and I). The distribution of Celsr3 and Fzd3 transcripts within the developing gut (arrows) is very similar to that of Ret mRNA, indicating that these genes are specifically expressed by enteric neural crest derivatives. Note that Cels3 and Fzd3 appear to label only a subset of cells marked with the Ret riboprobe. Scale bars: 100 μm.