Recent advances in neuroscience have implicated that a variety of key regulatory proteins, such as neurotrophins, ciliary neurotrophic factor (CNTF), agrin and neuregulin, play crucial roles in the regulation of neuronal development, and particularly, the formation of neuromuscular junction. Precise delineation of the potential targets of direct action of these regulatory factors requires the determination of the expression profile of these factors as well as their receptors. The present study provided the first systematic examination of the temporal and spatial expression profile of neurotrophins, CNTF, agrin as well as their receptors during development and following nerve injury. Our results demonstrated that both the temporal and spatial expression of neurotrophins, CNTF, agrin and...[ Read more ]

Recent advances in neuroscience have implicated that a variety of key regulatory proteins, such as neurotrophins, ciliary neurotrophic factor (CNTF), agrin and neuregulin, play crucial roles in the regulation of neuronal development, and particularly, the formation of neuromuscular junction. Precise delineation of the potential targets of direct action of these regulatory factors requires the determination of the expression profile of these factors as well as their receptors. The present study provided the first systematic examination of the temporal and spatial expression profile of neurotrophins, CNTF, agrin as well as their receptors during development and following nerve injury. Our results demonstrated that both the temporal and spatial expression of neurotrophins, CNTF, agrin and/or their receptors were developmentally regulated in rat. As an effort to expand our knowledge on the CNTF receptor in the avian system, we cloned the full length cDNA sequence encoding for the chick CNTF receptor α (CNTFRα) by screening a chick cDNA library. Interestingly, we found that the regulatory pattern of the expression of chick CNTFRα following nerve injury was different from that observed in rat. Our findings suggest that although CNTFRα may be important for regeneration in both rat and chick, the precise molecular mechanisms involved in this process might be different. The expression profile of another key receptor present in skeletal muscle, muscle specific kinase (MuSK), was also examined. MuSK has been recently suggested to be the key signaling component of the receptor complex of agrin. We found that the expression profile of MuSK in chick during development as well as following nerve injury was similar to that observed for rat. MuSK mRNA expression was also found to be regulated by electrical activity and ARIA. Taken together, our study provided the complete spatial and temporal spectra of the potential targets of neurotrophins, CNTF and agrin during neuronal development. The information gathered from our study provides insight into the possibility that CNTF and agrin may play essential roles in the regulation of denervation and regeneration.