A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans

15 páginas, 7 figuras, 3 tablas.

Detalles Bibliográficos
Autores: Doitsidou, Maria, Flames, Nuria, Topalidou, Irini, Abe, Namiko, Felton, Terry, Remesal, Laura, Popovitchenko, Tatiana, Mann, Richard S., Chalfie, Martin, Hobert, Oliver
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/97345
Acceso en línea:http://hdl.handle.net/10261/97345
Access Level:acceso abierto
Palabra clave:cis-regulatory motif
Differentiation
Dopamine
Elegans
Homeodomain
Neuron
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spelling A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegansDoitsidou, MariaFlames, NuriaTopalidou, IriniAbe, NamikoFelton, TerryRemesal, LauraPopovitchenko, TatianaMann, Richard S.Chalfie, MartinHobert, Olivercis-regulatory motifDifferentiationDopamineElegansHomeodomainNeuron15 páginas, 7 figuras, 3 tablas.Terminal differentiation programs in the nervous system are encoded by cis-regulatory elements that control the expression of terminal features of individual neuron types. We decoded the regulatory information that controls the expression of five enzymes and transporters that define the terminal identity of all eight dopaminergic neurons in the nervous system of the Caenorhabditis elegans hermaphrodite. We show that the tightly coordinated, robust expression of these dopaminergic enzymes and transporters ("dopamine pathway") is ensured through a combinatorial cis-regulatory signature that is shared by all dopamine pathway genes. This signature is composed of an Ets domain-binding site, recognized by the previously described AST-1 Ets domain factor, and two distinct types of homeodomain-binding sites that act in a partially redundant manner. Through genetic screens, we identified the sole C. elegans Distalless/Dlx ortholog, ceh-43, as a factor that acts through one of the homeodomain sites to control both induction and maintenance of terminal dopaminergic fate. The second type of homeodomain site is a Pbx-type site, which is recognized in a partially redundant and neuron subtype-specific manner by two Pbx factors, ceh-20 and ceh-40, revealing novel roles of Pbx factors in the context of terminal neuron differentiation. Taken together, we revealed a specific regulatory signature and cognate, terminal selector-type transcription factors that define the entire dopaminergic nervous system of an animal. Dopaminergic neurons in the mouse olfactory bulb express a similar combinatorial transcription factor collective of Ets/Dlx/Pbx factors, suggesting deep phylogenetic conservation of dopaminergic regulatory programs.This work was funded by EMBO post-doctoral fellowships and Marie Curie Funds (to M.D. and N.F.), the New York Stem Cell Foundation Fellowships and the Spanish Government (SAF2011-26273) (to N.F), the NIH (R01NS039996-05; R01NS050266-03 to O.H.; R01GM30997 to M.C.; R01GM054510 to R.S.M.; and F32GM099160 to N.A.), and the Stavanger University Hospital (to M.D.). N.F is a NARSAD Young Investigator. O.H. is an Investigator of the Howard Hughes Medical Institute.Peer reviewedCold Spring Harbor Laboratory Press201420142013info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/97345reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx. doi.org/10.1101/gad.217224.113info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/973452026-05-22T06:33:51Z
dc.title.none.fl_str_mv A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans
title A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans
spellingShingle A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans
Doitsidou, Maria
cis-regulatory motif
Differentiation
Dopamine
Elegans
Homeodomain
Neuron
title_short A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans
title_full A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans
title_fullStr A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans
title_full_unstemmed A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans
title_sort A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans
dc.creator.none.fl_str_mv Doitsidou, Maria
Flames, Nuria
Topalidou, Irini
Abe, Namiko
Felton, Terry
Remesal, Laura
Popovitchenko, Tatiana
Mann, Richard S.
Chalfie, Martin
Hobert, Oliver
author Doitsidou, Maria
author_facet Doitsidou, Maria
Flames, Nuria
Topalidou, Irini
Abe, Namiko
Felton, Terry
Remesal, Laura
Popovitchenko, Tatiana
Mann, Richard S.
Chalfie, Martin
Hobert, Oliver
author_role author
author2 Flames, Nuria
Topalidou, Irini
Abe, Namiko
Felton, Terry
Remesal, Laura
Popovitchenko, Tatiana
Mann, Richard S.
Chalfie, Martin
Hobert, Oliver
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv cis-regulatory motif
Differentiation
Dopamine
Elegans
Homeodomain
Neuron
topic cis-regulatory motif
Differentiation
Dopamine
Elegans
Homeodomain
Neuron
description 15 páginas, 7 figuras, 3 tablas.
publishDate 2013
dc.date.none.fl_str_mv 2013
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/97345
url http://hdl.handle.net/10261/97345
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx. doi.org/10.1101/gad.217224.113
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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