Developmentally regulated expression and localization of dystrophin and utrophin in the human fetal brain.

Expression of dystrophin and the dystrophin-related protein utrophin has been studied in the human fetal brain both in vivo and in vitro. Results showed that both these proteins were developmentally regulated, even if their expression followed a different pattern. Utrophin was found since very early stages of development, reached a peak between week 15-20 of gestation, declining then, so that at week 32 was barely detectable. The protein was mainly found in neuronal cell bodies, partially associated to the plasma membrane, and in astrocytes cytoplasm. On the contrary, the brain form of dystrophin was first detectable at week 12, increased up to week 15 and then remained stable. Dystrophin localization was similar but not identical to utrophin. In neurons, it was also partially associated with the plasma membrane of cell body and axon hillock. However, the most was concentrated in the cytoplasm and in the processes, where it appeared associated to neurofilaments. Astrocytes were negative for brain dystrophin, but positive for the muscle isoform. Results suggest that utrophin and dystrophin are likely to play a key, though different, role in the immature brain. They help in understanding the basic mechanism(s) underlying cognition defects frequently observed in Duchenne and Becker dystrophic patients.