Zebrafish unplugged reveals a role for muscle-specific kinase homologs in axonal pathway choice.

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 Neurosci

journal_title

Nature neuroscience

authors

Zhang J,Lefebvre JL,Zhao S,Granato M

doi

10.1038/nn1350

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

1303-9

issue

12

eissn

1097-6256

issn

1546-1726

pii

nn1350

journal_volume

7

pub_type

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