Abstract: |
Serving as the primary conduit for communication between the nucleus and the cytoplasm, nuclear pore complexes (NPCs) impact nearly every cellular process. The extent to which NPC composition varies and the functional significance of such variation in mammalian development has not been investigated. Here we report that a null allele of mouse nucleoporin Nup133, a structural subunit of the NPC, disrupts neural differentiation. We find that expression of Nup133 is cell type and developmental stage restricted, with prominent expression in dividing progenitors. Nup133-deficient epiblast and ES cells abnormally maintain features of pluripotency and differentiate inefficiently along the neural lineage. Neural progenitors achieve correct spatial patterning in mutant embryos; however, they are impaired in generating terminally differentiated neurons, as are Nup133 null ES cells. Our results reveal a role for structural nucleoporins in coordinating cell differentiation events in the developing embryo. © 2008 Elsevier Inc. All rights reserved. |
Keywords: |
controlled study; protein expression; mutation; nonhuman; protein function; biological markers; animal cell; mouse; mammalia; animals; mice; allele; animal tissue; cells, cultured; cell division; embryo; embryonic stem cell; alleles; embryo development; embryo pattern formation; neural stem cell; cell differentiation; neurons; transcription, genetic; mice, inbred c57bl; cell lineage; cell type; stem cell; in situ hybridization; gene expression regulation, developmental; alkaline phosphatase; cyclin dependent kinase inhibitor 1b; mammal; stemcell; cytoplasm; stem cells; cellbio; devbio; embryo, mammalian; cell nucleus; fibroblast growth factor 5; pluripotent stem cell; cyclin d1; cell communication; nerve cell differentiation; cell activity; octamer transcription factor 4; developmental stage; transcription factor nanog; chromosome mapping; transcription factor otx2; nuclear pore complex proteins; mice, inbred c3h; cyclin d2; ectoderm; crosses, genetic; mice, congenic; nuclear pore; nucleoporin; nuclear pore complex; gastrula; nucleoporin 133
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