Figure 3. An allelic series of gpr126 parses direct versus indirect compound function.

(A) Molecular structure for screen hits (PubChem). (B) Schematic of gpr126 alleles, predicted proteins, phenotypes, and predicted drug functions based on mbp restoration. (C-U) Whole-mount in situ hybridization for mbp in wild-type (WT) or gpr126. Black arrows indicate PLLn. Fraction of gpr126 larvae with increased mbp is noted in upper right of each image. (C-G) mbp expression in control larvae. Note absence of PLLn mbp in gpr126^stl47, gpr126^st49, and gpr126^stl215 (D-F) and reduction in gpr126^st63 (G). (H-L) PLLn mbp expression is partially restored in gpr126^st49 (J), gpr126^stl215 (K), and gpr126^st63 (L) in 10 μM undecylenic acid. (M-Q) PLLn mbp is weakly increased in one larva for gpr126^st49 (O) and gpr126^stl215 (P) but strongly increased in gpr126^st63 (Q) with 10 μM naloxone. (R-U) mbp PLLn expression is increased across all alleles in 5 μM telmisartan-treated larvae.