The Groucho ortholog UNC-37 interacts with the short Groucho-like protein LSY-22 to control developmental decisions in C. elegans

Development. 2010 Jun;137(11):1799-805. doi: 10.1242/dev.046219. Epub 2010 Apr 28.


Transcriptional co-repressors of the Groucho/TLE family are important regulators of development in many species. A subset of Groucho/TLE family members that lack the C-terminal WD40 domains have been proposed to act as dominant-negative regulators of Groucho/TLE proteins, yet such a role has not been conclusively proven. Through a mutant screen for genes controlling a left/right asymmetric cell fate decision in the nervous system of the nematode C. elegans, we have retrieved loss-of-function alleles in two distinct loci that display identical phenotypes in neuronal fate specification and in other developmental contexts. Using the novel technology of whole-genome sequencing, we find that these loci encode the C. elegans ortholog of Groucho, UNC-37, and, surprisingly, a short Groucho-like protein, LSY-22, that is similar to truncated Groucho proteins in other species. Besides their phenotypic similarities, unc-37 and lsy-22 show genetic interactions and UNC-37 and LSY-22 proteins also physically bind to each other in vivo. Our findings suggest that rather than acting as negative regulators of Groucho, small Groucho-like proteins may promote Groucho function. We propose that Groucho-mediated gene regulatory events involve heteromeric complexes of distinct Groucho-like proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism*
  • Epistasis, Genetic
  • Gene Expression Regulation, Developmental
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Two-Hybrid System Techniques


  • Caenorhabditis elegans Proteins
  • Repressor Proteins
  • Transcription Factors
  • unc-37 protein, C elegans