Characterization of the expression of dystrophins and dystrophin-associated proteins during embryonic neural stem/progenitor cell differentiation.

ABSTRACT

Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutations in the dystrophin gene. Dystrophin is required for the organization of a complex consisting of dystroglycans, sarcoglycans, dystrobrevins and syntrophins, known as the dystrophin-associated proteins complex (DAPC). In addition to muscle degeneration, cognitive impairment has been reported in DMD patients. To characterize a suitable model for studying the embryonic cerebral functions of dystrophin, we analyzed the expression patterns of dystrophins/DAPC in undifferentiated and differentiated embryonic neural stem/progenitor cells (NSPC). We found that NSPC express mRNAs for dystrophins Dp427, Dp140, Dp71 and Dp40; ß-dystroglycan; α- and ß-dystrobrevin; α1-, ß1-, ß2- and γ2-syntrophin; and ß-, γ-, δ- and ε-sarcoglycan. Some of these were differentially regulated during neuronal or astrocytic differentiation. Interestingly, the protein expression levels of Dp140, ß-dystroglycan and α2-dystrobrevin were also differentially regulated. Additionally, we found that proliferating NSPC and differentiated neurons and astrocytes show immuno-positive staining for dystrophins and ß-dystroglycan. Our results show that dystrophins and DAPC components are expressed and regulated during the neuronal or astrocytic differentiation of NSPC, suggesting that these proteins may have different roles in the brain development.