The REF-1 family of bHLH transcription factors pattern C. elegans embryos through Notch-dependent and Notch-independent pathways
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Updated: Aug 17, 2026

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
Published on: December 12, 2019
Alexandre Neves1, James R Priess
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Abstract:
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.
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