Pharmacological inhibition of lysosomal exocytosis improves cartilage pathology in galnsm/m mutant cartilage. (A,B) Confocal images of fli1a:EGFP;BRE:dmKO-positive larvae show that treatment with 35 nM vacuolin-1 improves chondrocyte shape and increases BMP signaling within the central (A) and lateral (B) portions of Meckel's cartilage in galnsm/m mutants. Scale bars: 20 µm. (C,D) Graphs show quantitative measurements of cell shape and the level of vacuolation in chondrocytes within the central (C) and lateral (D) regions. Error bars=s.e.m. One-way ANOVA with Dunnett's multi-comparison correction, *P<0.05, **P<0.01, ***P<0.00, ****P<0.0001. (E,F) Graphs show the level of fluorescent intensity in dmKO-positive cells within the central (E) and lateral (F) regions. dmKO was normalized to the local EGFP level in the cell. Error bars=s.e.m. One-way ANOVA with Dunnett's multi-comparison correction, *P<0.05, **P<0.01, ****P<0.0001. (G) Confocal images of fli1a:EGFP;SBE:mCherry-positive larvae show that treatment with 35 nM vacuolin-1 increases TGFβ signaling. (H) Graphs show the level of fluorescent intensity in mCherry-positive cells within the central (left) and lateral (right) regions. mCherry was normalized to the local EGFP level in the cell. Error bars=s.e.m. One-way ANOVA with Dunnett's multi-comparison correction. *P<0.05, **P<0.01. (I) Graph shows the percentage of cells with a high versus medium level of fluorescent signal in treated and untreated larvae. Error bars=s.e.m. One-way ANOVA with Dunnett's multi-comparison correction, *P<0.05.
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