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Assay for rescue of the <italic>fr24</italic> strong allele distinguishes compounds likely to rescue downstream, or at the level of, the Adgrg6 receptor.(A) Section of the heatmap in Figure 5A showing the results for colforsin, dihydrofissinolide, deoxygedunin and carapin-8(9)-ene. (B) Enlargement of the cluster containing gedunin-related compounds (cluster two in Figures 4G and 5B), highlighting deoxygedunin, dihydrofissinolide and carapin-8(9)-ene. Compounds that rescued mbp expression are shown as larger nodes; compounds that did not rescue mbp expression are shown as smaller nodes. (C) (i–x) The inner ear at 4 dpf stained for vcanb. Lateral views; anterior to the left. Scale bar (applies to panels i–x): 50 µm. (i) adgrg6tb233c/DMSO mutant control. (ii – v) Treatment of adgrg6tb233c mutants with the compounds at 25 µM indicated was able to rescue the tb233c mutant ear phenotype to variable degrees. (vi) adgrg6fr24/DMSO mutant control. (vii–x) Treatment of adgrg6fr24 mutants with colforsin rescued otic vcanb expression in the fr24 allele, whereas treatment with dihydrofissinolide, deoxygedunin and carapin-8(9)-ene was unable to rescue the fr24 ear phenotype. (xi–xiv) Representation of the chemical structure of the four compounds tested. Note the structural similarity between deoxygedunin, dihydrofissinolide and carapin-8(9)-ene.
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