Genetic specification of left-right asymmetry in the diaphragm muscles and their motor innervation.

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.

journal_name

Elife

journal_title

eLife

authors

Charoy C,Dinvaut S,Chaix Y,Morlé L,Sanyas I,Bozon M,Kindbeiter K,Durand B,Skidmore JM,De Groef L,Seki M,Moons L,Ruhrberg C,Martin JF,Martin DM,Falk J,Castellani V

doi

10.7554/eLife.18481

subject

Has Abstract

pub_date

2017-06-22 00:00:00

issn

2050-084X

journal_volume

6

pub_type

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