Roles Of Id2/Id4 In Regulating Oligodendrocyte Development

Myelin sheathes ensure the rapid conduction of neural impulse and provide nutritional support for neurons.Myelin sheathes are formed by differentiated oligodendrocytes(OLs)in the central nervous system(CNS).Defects of OL development lead to various human neural disorders and even death,such as multiple sclerosis(MS).Recently studies also showed that newly formed myelin sheathes are required for motor skill learning,spatial and fear memory consolidation,and enhancing CNS myelination rescues the synaptic loss after chronic hypoxia.During OL development,the differentiation of OPCs into mature OLs is precisely controlled,to ensure a sufficient number of OPCs and a proper time for their differentiation,which is critical for animal survival.Previous studies have declared Id2 and Id4 as key factors for the negative regulation of OL differentiation.However,these conclusions were mainly based on the in vitro investigation.Thus,in this study,Id2 and Id4 knock out(KO)mice were used to explore the in vivo function of these two genes during OL development,with in situ hybridization,immunofluorescent staining,and chicken in ovo electroporation technologies.The results showed that:(1)Id2-KO mice display normal OPC generation and proliferation,but mild and transient precocity of OL differentiation;(2)Id4-KO mice show normal OL development;(3)Id2/Id4 double KO mice have similar phenotypes of OL differentiation with Id2-KO mice,denying the functional redundancy between these two genes in suppressing OL differentiation in vivo;(4)Unlike Id2,Id4 does not expressed in OPCs in vivo;(5)Forced expression of Id2 and Id4 in vivo indeed disturb the differentiation of OPCs in chicken spinal cords.Taken together,these data firstly provide the evidences that Id2 and Id4 are not involved in inhibiting OPC differentiation in vivo during animal development,providing new insights into the molecular regulation of the early stage of OL development.