TY - JOUR TI - Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis in Xenopus AU - Lambert, Francois M AU - Cardoit, Laura AU - Courty, Elric AU - Bougerol, Marion AU - Thoby-Brisson, Muriel AU - Simmers, John AU - Tostivint, Hervé AU - Le Ray, Didier A2 - Mason, Carol A VL - 7 PY - 2018 DA - 2018/05/30 SP - e30693 C1 - eLife 2018;7:e30693 DO - 10.7554/eLife.30693 UR - https://doi.org/10.7554/eLife.30693 AB - 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. KW - acetylcholine KW - motoneuron KW - xenopus KW - hindlimb KW - spinal cord KW - metamorphosis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -