title: Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation.
abstract: During the development of the vertebrate nervous system, neurogenesis is promoted by proneural bHLH proteins such as the neurogenins, which act as potent transcriptional activators of neuronal differentiation genes. The pattern by which these proteins promote neuronal differentiation is thought to be governed by inhibitors, including a class of transcriptional repressors called the WRPW-bHLH proteins, which are similar to Drosophila proteins encoded by hairy and genes in the enhancer of split complex (E-(SPL)-C). Here, we describe the isolation and characterization of Hes6, which encodes a novel WRPW-bHLH protein expressed during neurogenesis in mouse and Xenopus embryos. We show that Hes6 expression follows that of neurogenins but precedes that of the neuronal differentiation genes. We provide several lines of evidence to show that Hes6 expression occurs in developing neurons and is induced by the proneural bHLH proteins but not by the Notch pathway. When ectopically expressed in Xenopus embryos, Hes6 promotes neurogenesis. The properties 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.
authors.affiliation: The Salk Institute for Biological Studies, PO Box 85800, La Jolla, CA 92186-5800, USA.
authors.forename: N
authors.initials: N
authors.lastname: Koyano-Nakagawa
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Anderson
authors.forename: C
authors.initials: C
authors.lastname: Kintner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000601:surgery; D004625:Embryo, Nonmammalian; D005246:Feedback; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000166:cytology*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism*; D029867:Xenopus Proteins; D014982:Xenopus laevis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C486570:Hes6 protein, mouse; C101907:neurogenin, Xenopus