BACKGROUND: In multiple sclerosis, development of screening tools for 
remyelination-promoting molecules is timely.
OBJECTIVE: A Xenopus transgenic line allowing conditional ablation of 
myelinating oligodendrocytes has been adapted for in vivo screening of 
remyelination-favoring molecules.
METHODS: In this transgenic, the green fluorescent protein reporter is fused to 
E. coli nitroreductase and expressed specifically in myelinating 
oligodendrocytes. Nitroreductase converts the innocuous pro-drug metronidazole 
to a cytotoxin. Spontaneous remyelination occurs after metronidazole-induced 
demyelinating responses. As tadpoles are transparent, these events can be 
monitored in vivo and quantified. At the end of metronidazole-induced 
demyelination, tadpoles were screened in water containing the compounds tested. 
After 72 h, remyelination was assayed by counting numbers of oligodendrocytes 
per optic nerve.
RESULTS: Among a battery of molecules tested, siponimod, a dual agonist of 
sphingosine-1-phosphate receptor 1 and 5, was among the most efficient favoring 
remyelination. Crispr/cas9 gene editing showed that the promyelinating effect of 
siponimod involves the sphingosine-1-phosphate receptor 5.
CONCLUSION: This Xenopus transgenic line constitutes a simple in vivo screening 
platform for myelin repair therapeutics. We validated several known 
promyelinating compounds and demonstrated that the strong remyelinating efficacy 
of siponimod implicates the sphingosine-1-phosphate receptor 5.