Hairy2 functions through both DNA-binding and non DNA-binding mechanisms at the neural plate border in Xenopus.

The Xenopus helix-loop-helix transcription factor Hairy2 is essential for neural crest progenitor survival and maintains cells in a mitotic undifferentiated pre-neural crest state. However, its mode of action remains largely unknown. Here we show that a Hairy2 DNA-binding mutant is unable to promote cell survival and to upregulate the expression of early neural border genes but is capable to increase cell proliferation and to expand NC in late embryos. We found that Hairy2 transiently activates in a DNA-binding independent manner the expression of the Notch ligand Delta1 and that Delta1 is required for Hairy2 to promote cell proliferation and to expand NC. Finally, we provide evidence that Hairy2 induces Delta1 through the transcription factor Stat3. Together, these results suggest that Hairy2 has a dual mode of action and may function at the neural plate border through both a DNA-binding and a non-DNA-binding Stat3-Delta1 mediated mechanism.