The Role Of Mios In Myelination And Myelin Maintenance

Myelin is a specialized multilayered membrane structure wrapping and insulating around the axon of neurons.It can not only ensure the efficient and fast propagation of action potentials,but also provide nutrition to the neurons and maintain the integrity of the axon structure.So myelination is critical for the normal function of the central nervous system(CNS)in vertebrates.In CNS,oligodendrocyte precursor cells(OPCs)proliferate and migrate to the suitable location,then they differentiate into mature oligodendrocytes(OLs)and begin to wrap axonal fibers and form a myelin sheath.The entire cell development and myelination process are tightly regulated by many regulatory factors,but little is known about the regulation of developmental myelination by the intracellular signals.Our previous research found that the deletion of Mios(missing oocytes)gene in all neural stem cells can cause severe myelination defects in mice.But neural stem cells have the potential to differentiate into neurons,oligodendrocytes and astrocytes,the question is in which cell line does the Mios gene play a role in developmental myelination?In this paper,we examine the role of Mios gene,which is highly expressed in neuron and OLs according to our previous result,in myelination.So,we generate the genetic knockout mouse that specifically delete Mios gene in neurons or developmental OLs using CamK?-Cre or Olig2-Cre separately.Quantitative Real-time PCR,Western Blot analysis,immunofluorescence staining and histochemical staining were used to determine whether the ablation of Mios gene in neurons or in OLs lineage can cause mice deficits of myelination.Then we also explore the role of Mios gene in myelin maintenance using Tmem10-Cre drivers the deletion of Mios in mature OLs.Our results show that conditional ablation of Mios in developmental OLs lineage results in severe and permanent hypomyelination in mouse CNS,characterized by the decrease of the myelin associated gene and protein expression,hypomyelination and reduction of myelinated axons.Deletion of Mios in neurons or mature oligodendrocytes,in contrast,does not disrupt developmental myelination or myelin maintenance.Therefore,our studies suggest that the Mios gene is required for developmental myelination,but mature oligodendrocytes do not require Mios for myelin maintenance in the adult brain.And the regulation of Mios gene on the developmental myelin sheath is dependent on the autonomous regulation of oligodendrocytes,not the non-autonomous regulation in neurons.These studies further clarified the biological function of Mios gene in the regulation of myelination in different cell lineages in mammal,completed the exploration of the role of Mios in the development and maintenance of myelin in CNS,and laid the foundation for the further study of the cellular and molecular mechanisms of Mios on myelination.