Roles Of Endocytic Adaptor Numb In The Development Of Mouse Myelination

Background:The myelin sheath plays an important role in maintaining the stability of central nervous system(CNS).The development of oligodendrocyte(OLs)and myelin is regulated by various intrinsic and extrinsic factors.Although lots of extracellular signaling factors and transcription factors have been proved to be worked during the development of OLs and myelin,few signals which regulate extracellular and intracellular have been reported.Numb was first identified as a cell-fate determinant in Drosophila,which can maintain cell adhesion and the connection between cells.The function of maintaining cell adhesion is also very crucial in the development of OLs.However,the function of Numb in the development of OLs and myelin hasn't been reported before.Objective:To invest the functions of Numb in the development of OLs and myelin.Methods:At first,we generated conditional kockout mice that lacked Numb specifically in OLs using the Cre/loxP recombination system with Oligl-promoter.Then,we use electron microscope to invest the development of myelin in CNS,and the expression of various myelin proteins were detected by using Western Blot and immunocytochemistry.The expression of myelin proteins mRNA was detected by RT-PCR.Rotarod test wad conducted to invest the motor coordination of mice.Result:We found out that brain size and body weight of mouse hadn't been disrupted in Numb cKO mouse.However,we found myelination deficiency and downregulation of myelin relative protein expression in Numb cKO mouse;Numb cKO reduced the number of OLs in adult mouse.The differeation and maturation of OPCs had been influenced.We found the mRNA expression of myelin protein had been downregulated.The behavioral test showed no obvious difference.