title: Differential regulation of Hes/Hey genes during inner ear development.
abstract: Notch signaling plays a crucial role during inner ear development and regeneration. Hes/Hey genes encode for bHLH transcription factors identified as Notch targets. We have studied the expression and regulation of Hes/Hey genes during inner ear development in the chicken embryo. Among several Hes/Hey genes examined, only Hey1 and Hes5 map to the sensory regions, although with salient differences. Hey1 expression follows Jag1 expression except at early prosensory stages while Hes5 expression corresponds well to Dl1 expression throughout otic development. Although Hey1 and Hes5 are direct Notch downstream targets, they differ in the level of Notch required for activation. Moreover, they also differ in mRNA stability, showing different temporal decays after Notch blockade. In addition, Bmp, Wnt and Fgf pathways also modify Hey1 and Hes5 expression in the inner ear. Particularly, the Wnt pathway modulates Hey1 and Jag1 expression. Finally, gain of function experiments show that Hey1 and Hes5 cross-regulate each other in a complex manner. Both Hey1 and Hes5 repress Dl1 and Hes5 expression, suggesting that they prevent the transition to differentiation stages, probably by preventing Atoh1 expression. In spite of its association with Jag1, Hey1 does not seem to be instrumental for lateral induction as it does not promote Jag1 expression. We suggest that, besides being both targets of Notch, Hey1 and Hes5 are subject to a rather complex regulation that includes the stability of their transcripts, cross regulation and other signaling pathways.
authors.affiliation: Developmental Biology Unit, CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain.
authors.forename: Jelena
authors.initials: J
authors.lastname: Petrovic
authors.affiliation: Developmental Biology Unit, CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain.
authors.forename: Hector
authors.initials: H
authors.lastname: Gálvez
authors.affiliation: Developmental Biology Unit, CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Neves
authors.affiliation: Developmental Biology Unit, CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain.
authors.forename: Gina
authors.initials: G
authors.lastname: Abelló
authors.affiliation: Developmental Biology Unit, CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Giraldez
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002642:Chick Embryo; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism*; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D046509:Tissue Culture Techniques; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D000072099:Serrate-Jagged Proteins; D051153:Wnt Proteins
keywords: Wnt; hair cells; hearing; mRNA stability; notch