P31 Role of Ret in satellite cell myogenesis and facioscapulohumeral muscular dystrophy

disease and Walker-Warburg syndrome. Here we investigate the structural changes in muscle, eye and notochord of 3dpf zebrafish larvae, with particular emphasis on the basement membrane. Antisense oligonucleotide morpholinos were used to knock down FKRP and fukutin in wild type zebrafish. The morphants had abnormal muscle fibres, disrupted vertical myosepta and sarcolemma. The area of the notochord was observed to be smaller in all morphants when compared to controls. Electron microscopy revealed disturbances in all three layers that form the peri-notochord sheath including the basement membrane. Toluidine blue staining showed disorganised retinal layering in both morphants. Dysplasia of the lens was observed in most fukutin morphants and two FKRP morphants with a severe phenotype. Transmission electron microscopy studies revealed a homogenous perturbation across the inner limiting membranes of both morphants which may account for the lens dysplasia. The rod and cones in the photoreceptor cell layer were found in lower density in both morphants with the least density in fukutin knock-downs which may be as a result of a disrupted external limiting membrane. We therefore conclude that FKRP and fukutin are essential for the integrity of membranes in the eye, muscle and notochord of developing zebrafish larvae.