Aatyk Is A Novel Regulator Of Oligoden-Drocyte Differentiation And Myelination

Oligodendrocytes?OLs?are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials.The lack of function and myelin sheath of OLs cause a series of neurological diseases,such as multiple sclerosis.To explore the mechanism that involved in the process of differentiation and myelination of OLs offers a new solution for prevention and treating neurological diseases,undoubtedly.To identify candidate genes involved in OL myelinogenesis,we compared the mRNA array data from Nkx2.2 knockout mice with those from transgenic mice over expressing Nkx2.2,two mouse models in which the differentiation of OLs is promoted or delayed,respectively,and we found the axonal outgrowth regulatory molecule Aatyk?apoptosis-associated tyrosine kinase?was up-regulated with OL differentiation.We found the Aatyk mRNA started to be expressed around embryonic day 18.5?E18.5?in the spinal white matter and progressively increased thereafter.Aatyk costained wtih Olig2 in OLs in the corpus collosum of wild-type mice at P15.In addation,the Aatyk⁺cells in the white matter were completely lost in Olig1 ^Cre;Myrf-CKO mice.Together,these findings demonstrated that Aatyk is expressed in differentiating OLs in the CNS.What's more,Aatyk knockdown inhibited OLs differentiation and the expression of myelin genes in vitro.Moreover,Aatyk-deficiency maintained the proliferation status of OLs but did not affect their survival.As is known to all,Aatyk affects the formation of recycling endosomes.It's maybe due to that Aatyk-deficiency affects the formation of recycling endosomes,and thus upsets the balance between degradation and recycling for modulation of receptor levels on the cell surface such as GPR17,which is highly expressed in OPCs but down-regulated in mature OLs to ensure full myelination,and thereby,affect OL differentiation and myelination.Thus,Aatyk is essential for the differentiation of OLs.