ArticleDevelopment (Cambridge, England)2021
Agrin/Lrp4 signal constrains MuSK-dependent neuromuscular synapse development in appendicular muscle.
Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- The Motor Neuromuscular Axis: The Overlooked Element of Developmental Programming in Diabetes and Metabolic Syndrome.International journal of molecular sciences · 2026Review
- Sequence-based genome-wide association study reveals genetic and metabolic mechanisms underlying feed efficiency-related traits in beef cattle.Journal of animal science and biotechnology · 2026Article
- Alternative Splicing of SORBS1 Affects Neuromuscular Junction Integrity in Myotonic Dystrophy Type 1.Journal of cachexia, sarcopenia and muscle · 2025Article
- Gut-muscle axis crosstalk in age-related sarcopenia: mechanisms and therapeutic targets.Frontiers in microbiology · 2025Review
- Neuronal LRP4 directs the development, maturation, and cytoskeletal organization of peripheral synapses.bioRxiv : the preprint server for biology · 2023Article
- Target-selective vertebrate motor axon regeneration depends on interaction with glial cells at a peripheral nerve plexus.PLoS biology · 2023Article
- A glia cell dependent mechanism at a peripheral nerve plexus critical for target-selective axon regeneration.bioRxiv : the preprint server for biology · 2023Article
- Peripheral nerve development in zebrafish requires muscle patterning by tcf15/paraxis.Developmental biology · 2022Article
- Sorting nexin 17 increases low-density lipoprotein receptor-related protein 4 membrane expression: A novel mechanism of acetylcholine receptor aggregation in myasthenia gravis.Frontiers in immunology · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
The receptor tyrosine kinase MuSK, its co-receptor Lrp4 and the Agrin ligand constitute a signaling pathway that is crucial in axial muscle for neuromuscular synapse development, yet whether this pathway functions similarly in appendicular muscle is unclear. Here, using the larval zebrafish pectoral fin, equivalent to tetrapod forelimbs, we show that, similar to axial muscle, developing appendicular muscles form aneural acetylcholine receptor (AChR) clusters prior to innervation. As motor axons arrive, neural AChR clusters form, eventually leading to functional synapses in a MuSK-dependent manner. We find that loss of Agrin or Lrp4 function, which abolishes synaptic AChR clusters in axial muscle, results in enlarged presynaptic nerve regions and progressively expanding appendicular AChR clusters, mimicking the consequences of motoneuron ablation. Moreover, musk depletion in lrp4 mutants partially restores synaptic AChR patterning. Combined, our results provide compelling evidence that, in addition to the canonical pathway in which Agrin/Lrp4 stimulates MuSK activity, Agrin/Lrp4 signaling in appendicular muscle constrains MuSK-dependent neuromuscular synapse organization. Thus, we reveal a previously unappreciated role for Agrin/Lrp4 signaling, thereby highlighting distinct differences between axial and appendicular synapse development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.