Transmembrane receptor tyrosine kinases (RTKs) are known to play an essential role in the intercellular signaling pathways such as the induction of synapse-specific gene expression. Studies of the vertebrate skeletal neuromuscular junctions (NMJ) have shown that the formation and maintenance of synaptic specialisation's rely on the exchange of signals between the axon terminal and the muscle fiber. Both the RTKs utilized by the neurotrophins (Trks), and a recently discovered muscle-specific RTK (MuSK) have been suppected to be involved in the development and maturation of the neuromuscular junctions....[ Read more ]

Transmembrane receptor tyrosine kinases (RTKs) are known to play an essential role in the intercellular signaling pathways such as the induction of synapse-specific gene expression. Studies of the vertebrate skeletal neuromuscular junctions (NMJ) have shown that the formation and maintenance of synaptic specialisation's rely on the exchange of signals between the axon terminal and the muscle fiber. Both the RTKs utilized by the neurotrophins (Trks), and a recently discovered muscle-specific RTK (MuSK) have been suppected to be involved in the development and maturation of the neuromuscular junctions.

In order to examine the roles of both the Trks and MuSK during development and synaptogenesis, we have cloned their cDNAs from Xenopus laevis libraries. Xenopus was chosen for this study because of the wealth of information about the formation of the NMJ in this species. Northern blot analysis of the spatial pattern of trks expression detected 3 transcripts of 10.1 kb. 9.5 kb and 3 kb for trk C, two transcripts of 5.1 and 5.8 for trk B, and expression for trk A was below detectable level in adult Xenopus tissue. Developmental expression of trk A showed that it was maternally expressed and this result was reminiscent of the expression pattern for its congnate ligand NGF.

Northern blot analysis of the spatial pattern of MuSK expression indicated that there was only one major transcript of 6 kb in the adult frog and that this transcript contained the complete EC and TK domains of MuSK. In the embryo, two smaller truncated transcripts of 3 kb and 1.3 kb were detected, and their expression was first seen at stage 5 indicating that they were maternally expressed. During the period of tadpole stage 57 to adult, the limb was found to contain high MuSK expression and also express a fourth transcript of 4.4 kb. The transcript was demonstrated to lack a small region of the 5' end of the MuSK receptor. Using RT-PCR, an isoform for MuSK containing a 89 amino acid insertion was detected in stage 40 embryonic head. RT-PCR analysis also revealed that MuSK was also expressed in the adult brain and the developing head of stage 40 embryos, indicating that MuSK could also play a role in the central nervous system.