Cell Reports
Volume 29, Issue 5, 29 October 2019, Pages 1082-1098.e10
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Article
Interaction of Axonal Chondrolectin with Collagen XIXa1 Is Necessary for Precise Neuromuscular Junction Formation

https://doi.org/10.1016/j.celrep.2019.09.033Get rights and content
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Highlights

  • Chondrolectin (Chodl) facilitates axon growth and branching at synapses in zebrafish

  • Chodl restricts neuromuscular junction size across vertebrates

  • Lack of Chodl alters synaptic transmission

  • Chodl binds collagen XIXa1 at the cell surface

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.

Keywords

extracellular matrix
neuromuscular junction
zebrafish
CaP motor neurons
axon growth
synapse
stalled motor axons
muscle pioneer cells
horizontal myoseptum

Cited by (0)

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Senior author

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These authors contributed equally

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Present address: Center for Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, People’s Republic of China

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Present address: Max Planck Institute for the Science of Light, Staudtstraße 2, 91058 Erlangen, Germany

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Lead Contact