The splicing co-factor Barricade/Tat-SF1 is required for cell cycle and lineage progression in Drosophila neural stem cells

Development. 2017 Nov 1;144(21):3932-3945. doi: 10.1242/dev.152199. Epub 2017 Sep 21.


Stem cells need to balance self-renewal and differentiation for correct tissue development and homeostasis. Defects in this balance can lead to developmental defects or tumor formation. In recent years, mRNA splicing has emerged as an important mechanism regulating cell fate decisions. Here we address the role of the evolutionarily conserved splicing co-factor Barricade (Barc)/Tat-SF1/CUS2 in Drosophila neural stem cell (neuroblast) lineage formation. We show that Barc is required for the generation of neurons during Drosophila brain development by ensuring correct neural progenitor proliferation and differentiation. Barc associates with components of the U2 small nuclear ribonucleoprotein (snRNP) complex, and its depletion causes alternative splicing in the form of intron retention in a subset of genes. Using bioinformatics analysis and a cell culture-based splicing assay, we found that Barc-dependent introns share three major traits: they are short, GC rich and have weak 3' splice sites. Our results show that Barc, together with the U2 snRNP complex, plays an important role in regulating neural stem cell lineage progression during brain development and facilitates correct splicing of a subset of introns.

Keywords: Barricade; Brain development; Cell cycle; Drosophila; Intron retention; Splicing.

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Base Composition / genetics
  • Base Sequence
  • Body Patterning / genetics
  • Brain / anatomy & histology
  • Cell Count
  • Cell Cycle*
  • Cell Lineage*
  • Cell Proliferation
  • Clone Cells
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Knockdown Techniques
  • Introns / genetics
  • Mice
  • Models, Biological
  • Mutation / genetics
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Phenotype
  • Protein Binding
  • RNA Interference
  • RNA Splice Sites / genetics
  • Ribonucleoprotein, U2 Small Nuclear / metabolism
  • Time Factors
  • Transcription Factors / metabolism*


  • Barc protein, Drosophila
  • Drosophila Proteins
  • RNA Splice Sites
  • Ribonucleoprotein, U2 Small Nuclear
  • Tat-specific factor 1, mouse
  • Transcription Factors