Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner ear

Radosevic, Marija, 1978-; Robert Moreno, Alexandre; Coolen, Marion; Bally-Cuif, Laure; Alsina i Español, Berta

Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner ear

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dc.contributor.author Radosevic, Marija, 1978-ca
dc.contributor.author Robert Moreno, Alexandreca
dc.contributor.author Coolen, Marionca
dc.contributor.author Bally-Cuif, Laureca
dc.contributor.author Alsina i Español, Bertaca
dc.date.accessioned 2015-12-16T19:07:39Z
dc.date.available 2015-12-16T19:07:39Z
dc.date.issued 2011
dc.description.abstract Proper spatial control of neurogenesis in the inner ear ensures the precise innervation of mechanotransducing cells and the propagation of auditory and equilibrium stimuli to the brain. Members of the Hairy and enhancer of split (Hes) gene family regulate neurogenesis by inhibiting neuronal differentiation and maintaining neural stem cell pools in non-neurogenic zones. Remarkably, their role in the spatial control of neurogenesis in the ear is unknown. In this study, we identify her9, a zebrafish ortholog of Hes1, as a key gene in regulating otic neurogenesis through the definition of the posterolateral non-neurogenic field. First, her9 emerges as a novel otic patterning gene that represses proneural function and regulates the extent of the neurogenic domain. Second, we place Her9 downstream of Tbx1, linking these two families of transcription factors for the first time in the inner ear and suggesting that the reported role of Tbx1 in repressing neurogenesis is in part mediated by the bHLH transcriptional repressor Her9. Third, we have identified retinoic acid (RA) signaling as the upstream patterning signal of otic posterolateral genes such as tbx1 and her9. Finally, we show that at the level of the cranial otic field, opposing RA and Hedgehog signaling position the boundary between the neurogenic and non-neurogenic compartments. These findings permit modeling of the complex genetic cascade that underlies neural patterning of the otic vesicle.ca
dc.description.sponsorship M.R. was supported by an FPI fellowship from MICIIN and A.R.-M. from a JdC postdoctoral contract from MICINN. Grant support was from BFU2008-00714 from MICINN
dc.format.mimetype application/pdfca
dc.identifier.citation Radosevic M, Robert-Moreno A, Coolen M, Bally-Cuif L, Alsina B. Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner ear. Development. 2011;138(3):397-408. DOI: 10.1242/dev.056093ca
dc.identifier.doi http://dx.doi.org/10.1242/dev.056093
dc.identifier.issn 0950-1991
dc.identifier.uri http://hdl.handle.net/10230/25453
dc.language.iso engca
dc.publisher Company of Biologistsca
dc.relation.ispartof Development. 2011;138(3):397-408
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.keyword HES
dc.subject.keyword Retinoic acid (RA) signaling
dc.subject.keyword Tbx1
dc.subject.keyword Neurogenesis
dc.subject.keyword Proneural
dc.subject.keyword Sensory organs
dc.subject.keyword Zebrafish
dc.subject.keyword Inner ear
dc.subject.other Peixos zebra -- Embrions -- Anatomiaca
dc.subject.other Laberint (Orella)ca
dc.title Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner earca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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