Loss of zygotic NUP107 protein causes missing of pharyngeal skeleton and other tissue defects with impaired nuclear pore function in zebrafish embryos

J Biol Chem. 2012 Nov 2;287(45):38254-64. doi: 10.1074/jbc.M112.408997. Epub 2012 Sep 10.

Abstract

The Nup107-160 multiprotein subcomplex is essential for the assembly of nuclear pore complexes. The developmental functions of individual constituents of this subcomplex in vertebrates remain elusive. In particular, it is unknown whether Nup107 plays an important role in development of vertebrate embryos. Zebrafish nup107 is maternally expressed and its zygotic expression becomes prominent in the head region and the intestine from 24 h postfertilization (hpf) onward. In this study, we generate a zebrafish mutant line, nup107(tsu068Gt), in which the nup107 locus is disrupted by an insertion of Tol2 transposon element in the first intron and as a result it fails to produce normal transcripts. Homozygous nup107(tsu068Gt) mutant embryos exhibit tissue-specific defects after 3 days postfertilization (dpf), including loss of the pharyngeal skeletons, degeneration of the intestine, absence of the swim bladder, and smaller eyes. These mutants die at 5-6 days. Extensive apoptosis occurs in the affected tissues, which is partially dependent on p53 apoptotic pathways. In cells of the defective tissues, FG-repeat nucleoporins are disturbed and nuclear pore number is reduced, leading to impaired translocation of mRNAs from the nucleus to the cytoplasm. Our findings shed new light on developmental function of Nup107 in vertebrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apoptosis / genetics
  • Chondrogenesis / genetics
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism*
  • Eye Abnormalities / embryology
  • Eye Abnormalities / genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Intestinal Mucosa / metabolism
  • Intestines / abnormalities
  • Male
  • Microscopy, Confocal
  • Mutation
  • Nuclear Pore / metabolism*
  • Nuclear Pore / physiology
  • Nuclear Pore Complex Proteins / genetics*
  • Nuclear Pore Complex Proteins / metabolism
  • Pharynx / abnormalities
  • Pharynx / metabolism*
  • RNA Transport / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism
  • Zygote / metabolism

Substances

  • NUP107 protein, zebrafish
  • Nuclear Pore Complex Proteins
  • RNA, Messenger
  • Zebrafish Proteins
  • Green Fluorescent Proteins