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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Zhang J,Lefebvre JL,Zhao S,Granato Mdoi
10.1038/nn1350subject
Has Abstractpub_date
2004-12-01 00:00:00pages
1303-9issue
12eissn
1097-6256issn
1546-1726pii
nn1350journal_volume
7pub_type
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