The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling

The generation of sensory neurons and hair cells of the inner ear is under tight control. Different members of the Hairy and Enhancer of Split genes (HES) are expressed in the inner ear, their full array of functions still not being disclosed. We have previously shown that zebrafish her9 acts as a p...

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Detalhes bibliográficos
Autores: Radosevic, Marija, 1978-, Fargas Madriles, Laura, 1989-, Alsina i Español, Berta
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/23646
Acesso em linha:http://hdl.handle.net/10230/23646
http://dx.doi.org/10.1371/journal.pone.0109860
Access Level:acceso abierto
Palavra-chave:Laberint (Orella) -- Anatomia
Neurobiologia del desenvolupament
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spelling The role of her4 in inner ear development and its relationship with proneural genes and Notch signallingRadosevic, Marija, 1978-Fargas Madriles, Laura, 1989-Alsina i Español, BertaLaberint (Orella) -- AnatomiaNeurobiologia del desenvolupamentThe generation of sensory neurons and hair cells of the inner ear is under tight control. Different members of the Hairy and Enhancer of Split genes (HES) are expressed in the inner ear, their full array of functions still not being disclosed. We have previously shown that zebrafish her9 acts as a patterning gene to restrict otic neurogenesis to an anterior domain. Here, we disclose the role of another her gene, her4, a zebrafish ortholog of Hes5 that is expressed in the neurogenic and sensory domains of the inner ear. The expression of her4 is highly dynamic and spatiotemporally regulated. We demonstrate by loss of function experiments that in the neurogenic domain her4 expression is under the regulation of neurogenin1 (neurog1) and the Notch pathway. Moreover, her4 participates in lateral inhibition during otic neurogenesis since her4 knockdown results in overproduction of the number of neurog1 and deltaB-positive otic neurons. In contrast, during sensorigenesis her4 is initially Notch-independent and induced by atoh1b in a broad prosensory domain. At later stages her4 expression becomes Notch-dependent in the future sensory domains but loss of her4 does not result in hair cell overproduction, suggesting that there other her genes can compensate its function.This work was supported by BFU2011-27006 from Ministerio de Ciencia e Innovacion (http://www.idi.mineco.gob.es/), MR was supported by FPI fellowship from Ministerio de Ciencia e Innovacion and LF was supported by FI from Agencia de gestio d’Ajuts Universitaris de Recerca(http://www10.gencat.cat/agaur_web/AppJava/catala/index.jsp).Public Library of Science (PLoS)201520152014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23646http://dx.doi.org/10.1371/journal.pone.0109860reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésPLoS ONE. 2014;9(10):e109860info:eu-repo/grantAgreement/ES/3PN/BFU2011-27006© 2014 Radosevic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/236462026-05-29T05:05:01Z
dc.title.none.fl_str_mv The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling
title The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling
spellingShingle The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling
Radosevic, Marija, 1978-
Laberint (Orella) -- Anatomia
Neurobiologia del desenvolupament
title_short The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling
title_full The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling
title_fullStr The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling
title_full_unstemmed The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling
title_sort The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling
dc.creator.none.fl_str_mv Radosevic, Marija, 1978-
Fargas Madriles, Laura, 1989-
Alsina i Español, Berta
author Radosevic, Marija, 1978-
author_facet Radosevic, Marija, 1978-
Fargas Madriles, Laura, 1989-
Alsina i Español, Berta
author_role author
author2 Fargas Madriles, Laura, 1989-
Alsina i Español, Berta
author2_role author
author
dc.subject.none.fl_str_mv Laberint (Orella) -- Anatomia
Neurobiologia del desenvolupament
topic Laberint (Orella) -- Anatomia
Neurobiologia del desenvolupament
description The generation of sensory neurons and hair cells of the inner ear is under tight control. Different members of the Hairy and Enhancer of Split genes (HES) are expressed in the inner ear, their full array of functions still not being disclosed. We have previously shown that zebrafish her9 acts as a patterning gene to restrict otic neurogenesis to an anterior domain. Here, we disclose the role of another her gene, her4, a zebrafish ortholog of Hes5 that is expressed in the neurogenic and sensory domains of the inner ear. The expression of her4 is highly dynamic and spatiotemporally regulated. We demonstrate by loss of function experiments that in the neurogenic domain her4 expression is under the regulation of neurogenin1 (neurog1) and the Notch pathway. Moreover, her4 participates in lateral inhibition during otic neurogenesis since her4 knockdown results in overproduction of the number of neurog1 and deltaB-positive otic neurons. In contrast, during sensorigenesis her4 is initially Notch-independent and induced by atoh1b in a broad prosensory domain. At later stages her4 expression becomes Notch-dependent in the future sensory domains but loss of her4 does not result in hair cell overproduction, suggesting that there other her genes can compensate its function.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/23646
http://dx.doi.org/10.1371/journal.pone.0109860
url http://hdl.handle.net/10230/23646
http://dx.doi.org/10.1371/journal.pone.0109860
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLoS ONE. 2014;9(10):e109860
info:eu-repo/grantAgreement/ES/3PN/BFU2011-27006
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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