The Role Of MeCP2in Neural Development And Underlying Mechanism

Rett Syndrome (RTT) is an X-linked dominant progressive debilitating neurodevelopmental disorder causing severe mental retardation predominantly in females. Mutations in the gene Methyl-CpG-binding protein-2(MeCP2) were discovered to be the primary cause. In order to study the function of MeCP2in neural development, NPCs were infected by retroviruses to generate MeCP2overexpression and knockdown, and further differentiated into neurons and astrocytes. Immunocytochemical staining showed MeCP2overexpression lead to more DCX+neurons in neural differentiation, and MeCP2knockdown introduced more GFAP+astrocytes in astrocytic differentiation, indicating MeCP2affected the fate choice process of neural precursor cells. Measurement of neurite number and length indicated MeCP2played an important role in neuron morphology and neurite formation. Further study with western blot and immunopercipitation illustrated MeCP2interfered the phospholation of Stat3and GFAP expression. We suggest MeCP2may inhibit the expression of GFAP, and thus suppresses gliogenesis, through interfering Jak-Stat pathway.