The REF-1 family of bHLH transcription factors pattern C. elegans embryos through Notch-dependent and Notch-independent pathways.
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.
Neves
Alexandre
A
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Priess
James R
JR
D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian; D005455:Fluorescent Antibody Technique / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology; D016296:Mutagenesis / Q000502:physiology; D012330:RNA, Double-Stranded / Q000378:metabolism; D051880:Receptors, Notch; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D012330:RNA, Double-Stranded; D051880:Receptors, Notch; D014157:Transcription Factors; C497759:N protein, Drosophila; C428453:ref-1 protein, C elegans