Exploring The Function Of Nucleoporin Seh1 In Mouse Neural Stem Cells

Nuclear pore complexs(NPCs)mediates macromolecules transportation between cytoplasm and nucleus,which is composed of about 30 different nucleoporins.Nucleoporins participate a set of physiological reactions and regulate various signaling pathway,and Nup107-160 subcomplex plays a central role as a scaffold of nuclear pore complex.Nucleoporin sehl is a member of Nup107-160 subcomplex,however,we had a limited knowledge about its function.Although it has been reported that sehl is involved in oogenesis of Drosophila,there is few studies about sehl in mammalians and humans.Recently,Hassan reported six candicate genes related to microcephaly,including seh1,although no variants were found in exonal sequence,we could not rule out the possibility that there is a functional changes in regulatory region.This study suggest that sehl may play a central role in central nervous system.Here we reported the nucleoporin sehl has a higher expression level in central nervous system,and we found that sehl expression levels in cortex and spinal cord increased during the mouse development,respectively.The result indicate that sehl may have a regulatory role in mouse neural development.Since traditional knockout of sehl in mice is embryonic lethal,we constructed hGFAP promoter driven-cre knockout mice,which specificly knockout sehl in neural stem cells,so that we can study the effect of sehl deficiency in central nervous system during mouse development.The mutant mice display a set of phenotype of paralysis,epilepsy,hyperspasmia,and a smaller brain,thinner cortex and olfactory bulb.The similar phenomenon has been observed in nestin promoter driven-cre knockout mice.The result illustrate that sehl is indispensable during mouse development.Through analysis of neural markers,we found a shortage of neuron and its precursor including an increase of astrocyte in cortex of mutant mice,with reduced oligodendrocyte in corpus callosum.However,mutant neural stem cell proliferate more than control.We inferred that sehl deficient neural stem cells cannot migrate and differentiate normaly into its progeny.We also studied the fuction of sehl in adult neural stem cells,and we do not find loss of sehl take effect on its differentiation and migration but proliferation of neural stem cells increased.