Explore The Role Of Nucleoporin Seh1 In The Development Of Oligodendrocyte

More and more studies have shown that nuclear pore complexs(NPC)participate in nucleocytoplasmic transport,gene transcription regulation,DNA damage repair,cell cycle regulation,and plays an important role in nervous system development.Neuronal precursors that lost Nup133 retain totipotency and can not produce normal terminal differentiated cells--neurons.The same as Nupl33,seh1 is a component of Nup107-160 sub-complex,belonging to the nuclear pore scaffold protein.So we assume that they may have the same function--participate in the regulation of the central nervous system development.There is no report on the role of sehl in mammalian development.Traditional knockout of sehl have caused mouse embryonic lethal,therefore,we chose to use the Cre/LoxP recombination system to study the role of sehl in oligodendrocyte development.Our results suggest that after conditional ablation of sehl in the oligodendrocyte precursor cells(OPC),the experimental group were born at the expected Mendelian frequency,but at postnatal Day 10,they developed myelin-deficient symptoms,such as tremor,seizures,and died at aboutl4 days of age.Anatomical experiments showed that the optic nerve of experimental group mice is almost translucent.Electron microscopy results further showed that the axons of the optic nerve and the spinal cord of the mutant mice are in a bare state and almost no mature myelin was observed.We further demonstrated that the absence of myelin was caused by loss of a large number of oligodendrocytes.However there was no significant cell death in the development of the entire oligodendrocyte lineage,and that the number of OPC did not change,and the development of astrocytes and neurons was not affected.So it suggested that the differentiation of oligodendrocyte precursor cell to mature oligodendrocyte was arrested.Subsequent mechanism explorations demonstrated that the expression of differentiation factors sox10 and olig2 was significantly down-regulated at protein level during the development of oligodendrocytes,however there were no significant changes in the differentiation inhibitory factors id2,id4,hesl and hes5.The cellular distribution of these promoting factors may be affected after sehl knockdown.But knock-down of sehl in oli-neu cells did not affect the expression of other nucleoporins,or mRNA distribution neither.The nuclear import and export of proteinis was also normal.We have demonstrated that the nucleoporin sehl is necessary for myelination,and has an irreplaceable role in the development of the oligodendrocyte and provides a basis for subsequent experiments.