Fig. 1

Schematic of zebrafish Adgrg6 alleles and the LOPAC screening pipeline. (A) Schematic of the Adgrg6 protein and the following domains: Signal peptide (SP), complement C1r/C1s, Uegf, BMP1 (CUB), pentraxin (PTX), sperm protein, enterokinase, and agrin (SEA), hormone receptor (HormR), GPCR autoproteolysis-inducing (GAIN), Stachel sequence (S), and 7-pass transmembrane (7TM) (for details, see references in.8 The GPCR autoproteolytic site (GPS) is shown (black arrow). The position of the amino acid change in the tb233c allele is shown,10 together with other alleles3, 10, 16 discussed in the text. Hypomorphic missense alleles and the amino acid changes are shown above in black; truncating nonsense mutations are shown in red. (B) Schematic of the screening pipeline. The LOPAC library was screened on homozygous adgrg6tb233c−/− hypomorphic mutant zebrafish embryos. Initially, all compounds were tested using the primary vcanb screen (blue) followed by two retests. Confirmed hits and some additional selected compounds (see text) were then tested in an optimized counter screen for mbp expression (orange). Images show the expression of vcanb in the developing inner ear (lateral views with anterior to the left and dorsal to the top, taken from Diamantopoulou et al.23) and mbp expression in the posterior lateral line ganglia (arrowheads) and nerves (dorsal views of the embryo; anterior to the left). Scores shown below the images were assigned as described previously.23 Scale bars: vcanb images, 50 μm; mbp images, 100 μm.