DEVELOPMENTAL EXPRESSION OF DYSTROPHIN, DYSTROPHIN-ASSOCIATED GLYCOPROTEINS AND OTHER MEMBRANE CYTOSKELETAL PROTEINS IN HUMAN SKELETAL AND HEART-MUSCLE

Dystrophin, utrophin and the dystrophin-associated glycoproteins, beta -dystroglycan and adhalin, were analyzed, together with the membrane c ytoskeletal proteins beta-spectrin, vinculin and talin, and adult and fetal myosin heavy chains, in 25 normal human fetuses from 8 to 24 wee ks of gestation. Dystrophin was present in heart and skeletal muscle f rom 8 weeks although in the latter was mainly in the cytoplasm at this stage. Utrophin expression increased until around gestational weeks 1 9/21, but by 24 weeks immunostaining and immunoblot band intensities h ad reduced. Beta-dystroglycan was scarce in skeletal muscle at 8 weeks , increased with maturation and was more abundant in heart of the same age. Adhalin appeared later than beta-dystroglycan on skeletal muscle fiber surfaces, positivity became more intense as the fibers matured. In heart adhalin was detectable only in groups of cells at 12-16 week s. From 8 weeks all fetal myotubes expressed beta-spectrin on their su rfaces, while vinculin and talin positivity was mainly at the peripher y of the fascicles, increasing with age. Adult slow myosin was seen in most myotubes al 10 weeks. Secondary myotubes then formed which incre asingly expressed adult fast myosin, while still retaining fetal myosi n. By 24 weeks most fibers expressing adult slow myosin had lost fetal myosin and were more mature in the expression of most membrane protei ns. Muscle membrane organization during human fetal development is a c omplex process and takes place earlier in heart than skeletal muscle.