title: Expression dynamics and functions of Hes factors in development and diseases.
abstract: Hes genes, encoding basic helix-loop-helix (HLH) transcriptional repressors, are mammalian homologues of Drosophila hairy and Enhancer of split genes, both of which are required for normal neurogenesis in Drosophila. There are seven members in the human Hes family, Hes1-7, which are expressed in many tissues and play various roles mainly in development. All Hes proteins have three conserved domains: basic HLH (bHLH), Orange, and WRPW domains. The basic region binds to target DNA sequences, while the HLH region forms homo- and heterodimers with other bHLH proteins, the Orange domain is responsible for the selection of partners during heterodimer formation, and the WRPW domain recruits corepressors. Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling, which regulates cell differentiation via cell-cell interaction. Hes factors regulate many events in development by repressing the expression of target genes, many of which encode transcriptional activators that promote cell differentiation. For example, Hes1, Hes3, and Hes5 are highly expressed by neural stem cells, and inactivation of these genes results in insufficient maintenance of stem cell proliferation and prematurely promotes neuronal differentiation. Recently, it was shown that the expression dynamics of Hes1 plays crucial roles in proper developmental timings and fate-determination steps of embryonic stem cells and neural progenitor cells. Here, we discuss some key features of Hes factors in development and diseases.
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Saitama, Japan. Electronic address: tkobayas@virus.kyoto-u.ac.jp.
authors.forename: Taeko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Saitama, Japan; World Premier International Research Initiative-Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan. Electronic address: rkageyam@virus.kyoto-u.ac.jp.
authors.forename: Ryoichiro
authors.initials: R
authors.lastname: Kageyama
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000254:growth & development; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004413:Dysostoses / Q000151:congenital / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D005810:Multigene Family; D012272:Ribs / Q000002:abnormalities / Q000378:metabolism; D012600:Scoliosis / Q000235:genetics / Q000378:metabolism; D013131:Spine / Q000002:abnormalities / Q000378:metabolism; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C495456:HES2 protein, human; C486601:HES7 protein, human; C489734:Hes1 protein, mouse; C078493:HES1 protein, human
keywords: Differentiation; Embryonic stem cells; Hes; Hes1 oscillation; Neural stem cells; Stem cells