Impact Of DDB1 On The Development Of Oligodendrocyte

Oligodendrocytes are an important type of glial cells in the central nervous system.During their lifetime,Oligodendrocytes have evolved from oligodendrocyte precursor cells to mature Oligodendrocytes through proliferation、migration and differentiation and eventually form Myelin sheath.After wrapping neuronal axons,myelin sheath can support axons and surrounding tissues,provide metabolic support for neurons,promote the transmission of action potential.DDB1(DNA damage-binding protein 1)is an evolutionarily conserved protein involved in many biological processes such as cell damage repair,cell cycle regulation and gene transcription.However,the role of DDB1 in the development of oligodendrocytes has not been demonstrated.We found that DDB1 was highly expressed in oligodendrocyte lineage cells.It has been reported that systemic deletion of Ddb1 in mice would cause early embryo death,so we conditionally knocked out Ddb1 in oligodendrocytes through the Cre/loxP recombinase system.Ddb1 cKO mice were born normally and were smaller than control mice,accompanied by tremors,convulsions,and abnormal hind limb movement.Mice began to die on the 12th day after birth.Our experiments demonstrated that the loss of DDB1 caused myelin sheath development disorders,significantly reduced the number of oligodendrocyte lineage cells and oligodendrocyte progenitor cells,affecting the formation of oligodendrocyte progenitor cells,leading to apoptosis and inhibiting cell differentiation,but did not affect cell proliferation.At the same time,we induced the knockout of Ddb1 in oligodendrocytes by tamoxifen,and observed the phenotypic phenomenon consistent with Ddb1 cKO mice.Finally,by overexpression and knockdown of Ddbl in primary rat oligodendrocytes in vitro,we again demonstrated that the deletion of DDB 1 in oligodendrocytes can lead to a decrease in the number of oligodendrocyte lineage cell,induce apoptosis and inhibit cell differentiation,but do not affect cell proliferation.