PMID- 15543140
OWN - NLM
STAT- MEDLINE
DCOM- 20050215
LR  - 20220309
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 7
IP  - 12
DP  - 2004 Dec
TI  - Zebrafish unplugged reveals a role for muscle-specific kinase homologs in axonal 
      pathway choice.
PG  - 1303-9
AB  - 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.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Department of Cell and Developmental Biology, University of Pennsylvania School 
      of Medicine, Philadelphia, Pennsylvania 19104-6058, USA.
FAU - Lefebvre, Julie L
AU  - Lefebvre JL
FAU - Zhao, Shuxia
AU  - Zhao S
FAU - Granato, Michael
AU  - Granato M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041114
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MuSK protein, zebrafish)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Zebrafish Proteins)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Axons/*physiology
MH  - Homeodomain Proteins/genetics/*physiology
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Neural Pathways/physiology
MH  - Receptor Protein-Tyrosine Kinases/genetics/*physiology
MH  - Receptors, Cholinergic/genetics/*physiology
MH  - Sequence Homology, Amino Acid
MH  - Zebrafish
MH  - Zebrafish Proteins/genetics/*physiology
EDAT- 2004/11/16 09:00
MHDA- 2005/02/16 09:00
CRDT- 2004/11/16 09:00
PHST- 2004/06/29 00:00 [received]
PHST- 2004/09/07 00:00 [accepted]
PHST- 2004/11/16 09:00 [pubmed]
PHST- 2005/02/16 09:00 [medline]
PHST- 2004/11/16 09:00 [entrez]
AID - nn1350 [pii]
AID - 10.1038/nn1350 [doi]
PST - ppublish
SO  - Nat Neurosci. 2004 Dec;7(12):1303-9. doi: 10.1038/nn1350. Epub 2004 Nov 14.