Nuclear pore composition regulates neural stem/progenitor cell differentiation in the mouse embryo.
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.
Lupu
Floria
F
Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Alves
Annabelle
A
Anderson
Kathryn
K
Doye
Valérie
V
Lacy
Elizabeth
E
D000483:Alleles; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004622:Embryo, Mammalian; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D022022:Nuclear Pore / Q000737:chemistry*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D014158:Transcription, Genetic
D015415:Biomarkers; D015778:Minor Histocompatibility Antigens; C529963:NUP133 protein, mouse; D028861:Nuclear Pore Complex Proteins