PUBLICATION
Zebrafish unplugged reveals a role for muscle-specific kinase homologs in axonal pathway choice
- Authors
- Zhang, J., Lefebvre, J.L., Zhao, S., and Granato, M.
- ID
- ZDB-PUB-041116-3
- Date
- 2004
- Source
- Nature Neuroscience 7(12): 1303-1309 (Journal)
- Registered Authors
- Granato, Michael, Lefebvre, Julie, Zhao, Shuxia
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Axons/physiology*
- Homeodomain Proteins/genetics
- Homeodomain Proteins/physiology*
- Molecular Sequence Data
- Mutation
- Neural Pathways/physiology
- Receptor Protein-Tyrosine Kinases/genetics
- Receptor Protein-Tyrosine Kinases/physiology*
- Receptors, Cholinergic/genetics
- Receptors, Cholinergic/physiology*
- Sequence Homology, Amino Acid
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- PubMed
- 15543140 Full text @ Nat. Neurosci.
Citation
Zhang, J., Lefebvre, J.L., Zhao, S., and Granato, M. (2004) Zebrafish unplugged reveals a role for muscle-specific kinase homologs in axonal pathway choice. Nature Neuroscience. 7(12):1303-1309.
Abstract
En route to their target, pioneering motor growth cones repeatedly encounter choice points at which they make pathway decisions. In the zebrafish mutant unplugged, two of the three segmental motor axons make incorrect decisions at a somitic choice point. Using positional cloning, we show here that unplugged encodes a homolog of muscle-specific kinase (MuSK) and that, unlike mammalian MuSK, unplugged has only a limited role in neuromuscular synaptogenesis. We demonstrate that unplugged is transiently expressed in cells adjacent to the choice point and that unplugged signaling before the arrival of growth cones induces changes in the extracellular environment. In addition, we find that the unplugged locus generates three different transcripts. The splice variant 1 (SV1) isoform lacks the extracellular modules essential for agrin responsiveness, and signaling through this isoform mediates axonal pathfinding, independent of the MuSK downstream component rapsyn. Our results demonstrate a new role for MuSK homologs in axonal pathway selection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping