| Summary: | Summary: 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. : The C-type lectin-domain-containing transmembrane molecule Chondrolectin (Chodl) is expressed by motor neurons. Oprişoreanu et al. show that binding of axonal Chodl to extracellular collagen XIXa1 is needed for proper neuromuscular junction differentiation in mice and zebrafish, as well as axon extension and branching at synapses in zebrafish. Keywords: extracellular matrix, neuromuscular junction, zebrafish, CaP motor neurons, axon growth, synapse, stalled motor axons, muscle pioneer cells, horizontal myoseptum
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