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

eLife

Valerie Castellani¹  Lies De Groef¹  Motoaki Seki²  Christiana Ruhrberg²  Donna M Martin³  Jennifer M Skidmore⁴  Julien Falk⁴  Lieve Moons⁵  James F Martin⁶  Camille Charoy⁷  Isabelle Sanyas⁷  Yohan Chaix⁷  Bénédicte Durand⁷  Muriel Bozon⁷  Laurette Morlé⁷  Karine Kindbeiter⁷  Sarah Dinvaut⁷ 

[1] Department of Communicable Diseases, University of Michigan Medical Center, Ann Arbor, United States;Animal Physiology and Neurobiology Section, Department of Biology, Laboratory of Neural Circuit Development and Regeneration, Leuven, Belgium;Baylor College of Medicine, Houston, United States;Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, United States;Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan;UCL Institute of Ophthalmology, University College London, London, United Kingdom;University of Lyon, Claude Bernard University Lyon 1, INMG UMR CNRS 5310, INSERM U1217, Lyon, France;

关键词: left/right asymmetry;    motoneuron;    diaphragm;    Nodal;    Slit/Robo;    axon guidance;   

DOI  :  10.7554/eLife.18481

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown