Figure 7: Disruption of the dynein-2 complex leads to aberrant Hedgehog signalling.
From: Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome
(a) Immunofluorescence micrographs of control and SRPS cells treated with SAG and stained for GLI3 (red), AcTUB (green) and 4,6-diamidino-2-phenylindole (blue). (b) DYNC2LI1/dynein-2 complex activity is required for the exclusion of SMO from the primary cilium in the absence of Hedgehog stimulation. Immunofluorescence micrographs of SAG-stimulated control and SRPS cells stained for SMO (green) and GluTUB (red). (c) Graph shows the mean percentage of ciliated cells with ciliary SMO±s.e.m. (>100 cells counted × three independent experiments). (d) Immunoblotting for GLI3 (full-length ‘GLI3FL’; repressor ‘GLI3R’) in cell extracts shows increased GLI3FL to GLI3R in SRPS cells. (e) Graph shows the ratio of GLI3FL to GLI3R. (f) Graph shows quantification of total GLI3 amounts (GLI3FL+GLI3R), which is increased in DYNC2LI1-mutant fibroblasts. Statistical analyses performed using Mann–Whitney test, *P<0.05. Scale bars, 5 μm.
