Otefin, a nuclear membrane protein, determines the fate of germline stem cells in Drosophila via interaction with Smad complexes

Dev Cell. 2008 Apr;14(4):494-506. doi: 10.1016/j.devcel.2008.02.018.


Nuclear envelope proteins play important roles in chromatin organization, gene regulation, and signal transduction; however, the physiological role of these proteins remains elusive. We found that otefin (ote), which encodes a nuclear lamin-binding protein [corrected], is essential for germline stem cell (GSC) maintenance. We show that Ote, as an intrinsic factor, is both necessary and sufficient to regulate GSC fate. Furthermore, we demonstrate that ote is required for the Dpp/BMP signaling pathway to silence bam transcription. By structure-function analysis, we demonstrate that the nuclear membrane localization of Ote is essential for its role in GSC maintenance. Finally, we show that Ote physically interacts with Medea/Smad4 at the bam silencer element to regulate GSC fate. Thus, we demonstrate that specific nuclear membrane components mediate signal-dependent transcriptional effects to control stem cell behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Cells, Cultured
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / anatomy & histology
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Female
  • Gene Silencing
  • Germ Cells / cytology
  • Germ Cells / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mutation
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Ovary / cytology
  • Ovary / metabolism
  • RNA Interference
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Signal Transduction / physiology
  • Smad4 Protein / genetics
  • Smad4 Protein / metabolism*
  • Stem Cells / cytology
  • Stem Cells / physiology*


  • Bone Morphogenetic Proteins
  • Drosophila Proteins
  • Med protein, Drosophila
  • Membrane Proteins
  • Nuclear Proteins
  • Ote protein, Drosophila
  • Recombinant Fusion Proteins
  • Smad4 Protein
  • bam protein, Drosophila
  • dpp protein, Drosophila