Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis in Xenopus

  1. Francois M Lambert  Is a corresponding author
  2. Laura Cardoit
  3. Elric Courty
  4. Marion Bougerol
  5. Muriel Thoby-Brisson
  6. John Simmers
  7. Hervé Tostivint
  8. Didier Le Ray
  1. CNRS Université de Bordeaux, France
  2. CNRS Muséum National d'Histoire Naturelle, France

Abstract

In vertebrates, functional motoneurons are defined as differentiated neurons that are connected to a central premotor network and activate peripheral muscle using acetylcholine. Generally, motoneurons and muscles develop simultaneously during embryogenesis. However, during Xenopus metamorphosis, developing limb motoneurons must reach their target muscles through the already established larval cholinergic axial neuromuscular system. Here, we demonstrate that at metamorphosis onset, spinal neurons retrogradely labeled from the emerging hindlimbs initially express neither choline acetyltransferase nor vesicular acetylcholine transporter. Nevertheless, they are positive for the motoneuronal transcription factor Islet1/2 and exhibit intrinsic and axial locomotor-driven electrophysiological activity. Moreover, the early appendicular motoneurons activate developing limb muscles via nicotinic antagonist-resistant, glutamate antagonist-sensitive, neuromuscular synapses. Coincidently, the hindlimb muscles transiently express glutamate, but not nicotinic receptors. Subsequently, both pre- and postsynaptic neuromuscular partners switch definitively to typical cholinergic transmitter signaling. Thus, our results demonstrate a novel context-dependent re-specification of neurotransmitter phenotype during neuromuscular system development.

Data availability

All data generated or analysed during this study are available via Dryad (doi:10.5061/dryad.9sj250q).

The following data sets were generated

Article and author information

Author details

  1. Francois M Lambert

    INCIA UMR 5287, CNRS Université de Bordeaux, Bordeaux, France
    For correspondence
    francois.lambert@u-bordeaux.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8655-2652
  2. Laura Cardoit

    INCIA UMR 5287, CNRS Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Elric Courty

    INCIA UMR 5287, CNRS Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Marion Bougerol

    ERE UMR 7221, CNRS Muséum National d'Histoire Naturelle, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Muriel Thoby-Brisson

    INCIA UMR 5287, CNRS Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3214-1724
  6. John Simmers

    INCIA UMR 5287, CNRS Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Hervé Tostivint

    ERE UMR 7221, CNRS Muséum National d'Histoire Naturelle, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Didier Le Ray

    INCIA UMR 5287, CNRS Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.

Funding

Centre National de la Recherche Scientifique

  • Didier Le Ray

Muséum National d'Histoire Naturelle (Actions thématiques du Museum)

  • Hervé Tostivint

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were carried out in accordance with, and approved by, the local ethics committee (protocols no. 68-019) to H. Tostivint and no. 2016011518042273 APAFIS no. 3612 to DLR)

Reviewing Editor

  1. Carol A Mason, Columbia University, United States

Publication history

  1. Received: July 25, 2017
  2. Accepted: May 6, 2018
  3. Accepted Manuscript published: May 30, 2018 (version 1)
  4. Version of Record published: June 12, 2018 (version 2)

Copyright

© 2018, Lambert et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Francois M Lambert
  2. Laura Cardoit
  3. Elric Courty
  4. Marion Bougerol
  5. Muriel Thoby-Brisson
  6. John Simmers
  7. Hervé Tostivint
  8. Didier Le Ray
(2018)
Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis in Xenopus
eLife 7:e30693.
https://doi.org/10.7554/eLife.30693
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    Funding: Deutsche Forschungsgesellschaft (410169619, 424778381), Deutsches Zentrum für Luftund Raumfahrt (DynaSti), National Institutes of Health (2R01 MH113929), Foundation for OCD Research (FFOR).