The REF-1 family of bHLH transcription factors pattern C. elegans embryos through Notch-dependent and Notch-independent pathways

Dev Cell. 2005 Jun;8(6):867-79. doi: 10.1016/j.devcel.2005.03.012.


Much of the patterning of early C. elegans embryos involves a series of Notch interactions that occur in rapid succession and have distinct outcomes; however, none of the targets for these interactions have been identified. We show that the REF-1 family of bHLH transcription factors is a major target of Notch signaling in all these interactions and that most examples of Notch-mediated transcriptional repression can be attributed to REF-1 activities. The REF-1 family is expressed and has similar functions in both Notch-dependent and Notch-independent pathways, and this dual mode of deployment is used repeatedly to pattern the embryo. REF-1 proteins are unusual in that they contain two different bHLH domains and lack the distinguishing characteristics of Hairy/Enhancer of Split (HES) bHLH proteins that are Notch targets in other systems. Our results show that the highly divergent REF-1 proteins are nonetheless HES-like bHLH effectors of Notch signaling.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Drosophila
  • Drosophila Proteins
  • Embryo, Nonmammalian
  • Fluorescent Antibody Technique / methods
  • Gene Expression Regulation, Developmental / physiology*
  • Membrane Proteins / physiology*
  • Models, Biological
  • Molecular Sequence Data
  • Morphogenesis / physiology
  • Mutagenesis / physiology
  • RNA, Double-Stranded / metabolism
  • Receptors, Notch
  • Sequence Alignment
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism*


  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Membrane Proteins
  • N protein, Drosophila
  • RNA, Double-Stranded
  • Receptors, Notch
  • Transcription Factors
  • ref-1 protein, C elegans