RT Journal Article SR Electronic T1 Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis in Xenopus JF bioRxiv FD Cold Spring Harbor Laboratory SP 173328 DO 10.1101/173328 A1 F. M. Lambert A1 L. Cardoit A1 E. Courty A1 M. Bougerol A1 M. Thoby-Brisson A1 J. Simmers A1 H. Tostivint A1 D. Le Ray YR 2017 UL http://biorxiv.org/content/early/2017/08/08/173328.abstract 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.