Paper entitled, "Zebrafish survival motor neuron Mutants Exhibit Presynaptic Neuromuscular Junction Defects" published in Human Molecular Genetics by FSMA-funded lead author Dr. Kum-Loong Boon from the laboratory of Dr. Christine Beattie at Ohio State University.

In this study the authors report the isolation and characterization of mutants in the zebrafish smn gene.  SMN mutants were smaller, but otherwise formed normally. The fish exhibited less activity before dying often lying at the bottom of their tank. The most striking neuromuscular defect in these fish was a decrease in the presynaptic protein SV2 in all mutants analyzed. This indicates that NMJs are not maintained when Smn levels are decreased and that there is less presynaptic protein at the NMJs.

The authors have previously shown that reducing Smn earlier in development caused defects in motor axonoutgrowth and decreased longevity. Taken together all of these data suggest that early depletion of Smn has more severe defects in zebrafish affecting the development of motor axons. Removing Smn after motor axon outgrowth and synapse formation, as is the situation in the smn mutants described in this paper, however affects the maintenance of the presynaptic terminal. Thus, in both scenarios motoneurons are affected but at difference stages, outgrowth and synaptic maintenance respectively. Interestingly, this also suggests that depleting Smn after motor axon outgrowth and synapse formation still has an effect on the NMJs. Thus the phenotypes exhibited strongly depend on the levels and timing of Smn protein expression.

Finally to further understand the neuronal specificity of SMA, we have generated transgenic fish that express human SMN (hSMN) only in motoneurons and then generated mutant lines carrying this transgene. Interestingly, the motoneuron- specific hSMN corrected the observed NMJ defect. Thus, we conclude that SMN in motoneurons is necessary for presynaptic NMJ integrity.