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Chondrolectin (Chodl) is needed for motor axon extension in zebrafish and is dysregulated in mouse models of spinal muscular atrophy (SMA). However, the mechanistic basis of Chodl function is not known. Here, we use Chodl-deficient zebrafish and mouse mutants to show that the absence of Chodl leads to anatomical and functional defects of the neuromuscular synapse. In zebrafish, the growth of an identified motor axon beyond an "en passant" synapse and later axon branching from synaptic points are impaired, leading to functional deficits. Mechanistically, motor-neuron-autonomous Chodl function depends on its intracellular domain and on binding muscle-derived collagen XIXa1 by its extracellular C-type lectin domain. Our data support evolutionarily conserved roles of Chodl in synaptogenesis and provide evidence for a "synapse-first" scenario of motor axon growth in zebrafish.

Original publication

DOI

10.1016/j.celrep.2019.09.033

Type

Journal article

Journal

Cell reports

Publication Date

10/2019

Volume

29

Pages

1082 - 1098.e10

Addresses

Centre for Discovery Brain Sciences, University of Edinburgh, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.

Keywords

Neurites, Axons, Motor Neurons, Neuromuscular Junction, Motor Endplate, Synapses, Animals, Zebrafish, Humans, Mice, Zebrafish Proteins, Lectins, C-Type, Fibril-Associated Collagens, Escape Reaction, Motor Activity, Evolution, Molecular, Gene Expression Regulation, Developmental, Conserved Sequence, Protein Binding, Larva, Phenotype, Mutation, Neurogenesis, Electrophysiological Phenomena, HEK293 Cells, Protein Domains