Mutations in a Guanylate Cyclase GCY-35/GCY-36 Modify Bardet-Biedl Syndrome–Associated Phenotypes in Caenorhabditis elegans
Figure 5
Multiple sensory neurons influence the body size of bbs mutants.
(A) The expression of wild-type BBS protein in body cavity neurons was insufficient to rescue body length defects of bbs-7 and bbs-2 mutants, while expression in other ciliated sensory neurons (light bars) restored body length. ANOVA with Tukey, *** p<0.001; ns – p≥0.05, n≥11. Data represent mean ± SD normalized against wild-type body length. (B) GCY-35, but not other GCY mutants, exhibited a strong suppression effect on bbs-7 mutant body length. Box and whisker plot of additional gcy mutants showing partially improved body length (light bars), decreased body length (black bars), and no change (dark bars) in comparison to bbs-7 mutants. Boxes represent 25th–75th percentile of populations with maximum and minimum values as whiskers. ANOVA with Tukey, *** p<0.001; ns – p≥0.05 compared to bbs-7 mutants. Data represent mean ± SD normalized against wild-type body length. (C–D) A model for ciliary and cGMP-mediated body size regulation. (C) GCY-35/GCY-36 activity produces cGMP in the body cavity neurons and activates EGL-4 to inhibit body size. This process is influenced by BBS proteins present in other ciliated sensory neurons. (D) Some ciliated sensory neurons producing other GCs undergo a BBS-independent EGL-4 activation to influence body size and developmental timing.