HRT1, HRT2, and HRT3: a new subclass of bHLH transcription factors marking specific cardiac, somitic, and pharyngeal arch segments.

Members of the Hairy/Enhancer of Split family of basic helix-loop-helix (bHLH) transcription factors are regulated by the Notch signaling pathway in vertebrate and Drosophila embryos and control cell fates and establishment of sharp boundaries of gene expression. Here, we describe a new subclass of bHLH proteins, HRT1 (Hairy-related transcription factor 1), HRT2, and HRT3, that share high homology with the Hairy family of proteins yet have characteristics that are distinct from those of Hairy and other bHLH proteins. Each HRT gene was expressed in distinct cell types within numerous organs, particularly in those patterned along the anterior-posterior axis. HRT1 and HRT2 were expressed in atrial and ventricular precursors, respectively, and were also expressed in the cardiac outflow tract and aortic arch arteries. HRT1 and HRT2 transcripts were also detected in precursors of the pharyngeal arches and subsequently in the pharyngeal clefts. Within somitic precursors, HRT1 and HRT3 exhibited dynamic expression in the presomitic mesoderm, mirroring the expression of other components of Notch-Delta signaling pathways. The HRT genes were expressed in other sites of epithelial-mesenchymal interactions, including the developing kidneys, brain, limb buds, and vasculature. The unique and complementary expression patterns of this novel subfamily of bHLH proteins suggest a previously unrecognized role for Hairy-related pathways in segmental patterning of the heart and pharyngeal arches, among other organs.