Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation

During the development of the vertebrate nervous system, neurogenesis is pr omoted by proneural bHLH proteins such as the neurogenins, which act as pot ent transcriptional activators of neuronal differentiation genes. The patte rn by which these proteins promote neuronal differentiation is thought to h e governed by inhibitors, including a class of transcriptional repressors c alled the WRPW-bHLH proteins, which are similar to Drosophila proteins enco ded hy hairy and genes in the enhancer of split complex (E-(SPL)-C). Here, we describe the isolation and characterization of Hes6, which encodes a nov el WRPW-bHLH protein expressed during neurogenesis in mouse and Xenopus emb ryos. We show that Hes6 expression follows that of neurogenins but precedes that of the neuronal differentiation genes. We provide several lines of ev idence to show that Hes6 expression occurs in developing neurons and is ind uced by the proneural bHLH proteins but not by the Notch pathway. When ecto pically expressed in Xenopus embryos, Hes6 promotes neurogenesis. The prope rties of Hes6 distinguish it from other members of the WRPW-bHLH family in vertebrates, and suggest that it acts in a positive-feedback loop with the proneural bHLH proteins to promote neuronal differentiation.