Charoy, C;
Dinvaut, S;
Chaix, Y;
Morlé, L;
Sanyas, I;
Bozon, M;
Kindbeiter, K;
... Castellani, V; + view all
(2017)
Genetic specification of left-right asymmetry in the diaphragm muscles and their motor innervation.
eLife
, 6
, Article e18481. 10.7554/eLife.18481.
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Abstract
The diaphragm muscle is essential for breathing in mammals. Its asymmetric elevation during contraction correlates with morphological features suggestive of inherent left-right (L/R) asymmetry. Whether this asymmetry is due to L versus R differences in the muscle or in the phrenic nerve activity is unknown. Here, we have combined the analysis of genetically modified mouse models with transcriptomic analysis to show that both the diaphragm muscle and phrenic nerves have asymmetries, which can be established independently of each other during early embryogenesis in pathway instructed by Nodal, a morphogen that also conveys asymmetry in other organs. We further found that phrenic motoneurons receive an early L/R genetic imprint, with L versus R differences both in Slit/Robo signaling and MMP2 activity and in the contribution of both pathways to establish phrenic nerve asymmetry. Our study therefore demonstrates L-R imprinting of spinal motoneurons and describes how L/R modulation of axon guidance signaling helps to match neural circuit formation to organ asymmetry.
| Type: | Article |
|---|---|
| Title: | Genetic specification of left-right asymmetry in the diaphragm muscles and their motor innervation. |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.18481 |
| Publisher version: | http://dx.doi.org/10.7554/eLife.18481 |
| Additional information: | Copyright Charoy et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Keywords: | Nodal, Slit/Robo, axon guidance, developmental biology, diaphragm, left/right asymmetry, motoneuron, mouse, neuroscience, stem cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1561379 |
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