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Publication : Diverging roles for Lrp4 and Wnt signaling in neuromuscular synapse development during evolution.

First Author  Remédio L Year  2016
Journal  Genes Dev Volume  30
Issue  9 Pages  1058-69
PubMed ID  27151977 Mgi Jnum  J:232554
Mgi Id  MGI:5779567 Doi  10.1101/gad.279745.116
Citation  Remedio L, et al. (2016) Diverging roles for Lrp4 and Wnt signaling in neuromuscular synapse development during evolution. Genes Dev 30(9):1058-69
abstractText  Motor axons approach muscles that are prepatterned in the prospective synaptic region. In mice, prepatterning of acetylcholine receptors requires Lrp4, a LDLR family member, and MuSK, a receptor tyrosine kinase. Lrp4 can bind and stimulate MuSK, strongly suggesting that association between Lrp4 and MuSK, independent of additional ligands, initiates prepatterning in mice. In zebrafish, Wnts, which bind the Frizzled (Fz)-like domain in MuSK, are required for prepatterning, suggesting that Wnts may contribute to prepatterning and neuromuscular development in mammals. We show that prepatterning in mice requires Lrp4 but not the MuSK Fz-like domain. In contrast, prepatterning in zebrafish requires the MuSK Fz-like domain but not Lrp4. Despite these differences, neuromuscular synapse formation in zebrafish and mice share similar mechanisms, requiring Lrp4, MuSK, and neuronal Agrin but not the MuSK Fz-like domain or Wnt production from muscle. Our findings demonstrate that evolutionary divergent mechanisms establish muscle prepatterning in zebrafish and mice.
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