A right-handed signalling pathway drives heart looping in vertebrates.

Most animals show external bilateral symmetry, which hinders the observation of multiple internal left-right (L/R) asymmetries that are fundamental to organ packaging and function. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand sid...

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Detalles Bibliográficos
Autores: Ocaña, Oscar H, Coskun, Hakan, Minguillón, Carolina, Murawala, Prayag, Tanaka, Elly M, Galcerán, Joan, Muñoz-Chápuli, Ramón, Nieto, M Angela
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17332
Acceso en línea:http://hdl.handle.net/20.500.12105/17332
Access Level:acceso abierto
Palabra clave:Actomyosin
Animals
Cell Movement
Chick Embryo
Epithelial-Mesenchymal Transition
Female
Heart
Homeodomain Proteins
Mesoderm
Mice
Morphogenesis
Myocardium
Signal Transduction
Snail Family Transcription Factors
Transcription Factors
Zebrafish
Zebrafish Proteins
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/17332
network_acronym_str ES
network_name_str España
repository_id_str
spelling A right-handed signalling pathway drives heart looping in vertebrates.Ocaña, Oscar HCoskun, HakanMinguillón, CarolinaMurawala, PrayagTanaka, Elly MGalcerán, JoanMuñoz-Chápuli, RamónNieto, M AngelaActomyosinAnimalsCell MovementChick EmbryoEpithelial-Mesenchymal TransitionFemaleHeartHomeodomain ProteinsMesodermMiceMorphogenesisMyocardiumSignal TransductionSnail Family Transcription FactorsTranscription FactorsZebrafishZebrafish ProteinsMost animals show external bilateral symmetry, which hinders the observation of multiple internal left-right (L/R) asymmetries that are fundamental to organ packaging and function. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand side by the epithelial-mesenchymal transition (EMT) inducer Snail1 (refs 3, 4). Despite some existing evidence, it remains unclear whether an equivalent instructive pathway provides right-hand-specific information to the embryo. Here we show that, in zebrafish, BMP mediates the L/R asymmetric activation of another EMT inducer, Prrx1a, in the lateral plate mesoderm with higher levels on the right. Prrx1a drives L/R differential cell movements towards the midline, leading to a leftward displacement of the cardiac posterior pole through an actomyosin-dependent mechanism. Downregulation of Prrx1a prevents heart looping and leads to mesocardia. Two parallel and mutually repressed pathways, respectively driven by Nodal and BMP on the left and right lateral plate mesoderm, converge on the asymmetric activation of the transcription factors Pitx2 and Prrx1, which integrate left and right information to govern heart morphogenesis. This mechanism is conserved in the chicken embryo, and in the mouse SNAIL1 acts in a similar manner to Prrx1a in zebrafish and PRRX1 in the chick. Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates.20242024-01-2320172017-09-0620172017-09-06research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/17332reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/173322026-06-12T12:43:37Z
dc.title.none.fl_str_mv A right-handed signalling pathway drives heart looping in vertebrates.
title A right-handed signalling pathway drives heart looping in vertebrates.
spellingShingle A right-handed signalling pathway drives heart looping in vertebrates.
Ocaña, Oscar H
Actomyosin
Animals
Cell Movement
Chick Embryo
Epithelial-Mesenchymal Transition
Female
Heart
Homeodomain Proteins
Mesoderm
Mice
Morphogenesis
Myocardium
Signal Transduction
Snail Family Transcription Factors
Transcription Factors
Zebrafish
Zebrafish Proteins
title_short A right-handed signalling pathway drives heart looping in vertebrates.
title_full A right-handed signalling pathway drives heart looping in vertebrates.
title_fullStr A right-handed signalling pathway drives heart looping in vertebrates.
title_full_unstemmed A right-handed signalling pathway drives heart looping in vertebrates.
title_sort A right-handed signalling pathway drives heart looping in vertebrates.
dc.creator.none.fl_str_mv Ocaña, Oscar H
Coskun, Hakan
Minguillón, Carolina
Murawala, Prayag
Tanaka, Elly M
Galcerán, Joan
Muñoz-Chápuli, Ramón
Nieto, M Angela
author Ocaña, Oscar H
author_facet Ocaña, Oscar H
Coskun, Hakan
Minguillón, Carolina
Murawala, Prayag
Tanaka, Elly M
Galcerán, Joan
Muñoz-Chápuli, Ramón
Nieto, M Angela
author_role author
author2 Coskun, Hakan
Minguillón, Carolina
Murawala, Prayag
Tanaka, Elly M
Galcerán, Joan
Muñoz-Chápuli, Ramón
Nieto, M Angela
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Actomyosin
Animals
Cell Movement
Chick Embryo
Epithelial-Mesenchymal Transition
Female
Heart
Homeodomain Proteins
Mesoderm
Mice
Morphogenesis
Myocardium
Signal Transduction
Snail Family Transcription Factors
Transcription Factors
Zebrafish
Zebrafish Proteins
topic Actomyosin
Animals
Cell Movement
Chick Embryo
Epithelial-Mesenchymal Transition
Female
Heart
Homeodomain Proteins
Mesoderm
Mice
Morphogenesis
Myocardium
Signal Transduction
Snail Family Transcription Factors
Transcription Factors
Zebrafish
Zebrafish Proteins
description Most animals show external bilateral symmetry, which hinders the observation of multiple internal left-right (L/R) asymmetries that are fundamental to organ packaging and function. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand side by the epithelial-mesenchymal transition (EMT) inducer Snail1 (refs 3, 4). Despite some existing evidence, it remains unclear whether an equivalent instructive pathway provides right-hand-specific information to the embryo. Here we show that, in zebrafish, BMP mediates the L/R asymmetric activation of another EMT inducer, Prrx1a, in the lateral plate mesoderm with higher levels on the right. Prrx1a drives L/R differential cell movements towards the midline, leading to a leftward displacement of the cardiac posterior pole through an actomyosin-dependent mechanism. Downregulation of Prrx1a prevents heart looping and leads to mesocardia. Two parallel and mutually repressed pathways, respectively driven by Nodal and BMP on the left and right lateral plate mesoderm, converge on the asymmetric activation of the transcription factors Pitx2 and Prrx1, which integrate left and right information to govern heart morphogenesis. This mechanism is conserved in the chicken embryo, and in the mouse SNAIL1 acts in a similar manner to Prrx1a in zebrafish and PRRX1 in the chick. Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-09-06
2017
2017-09-06
2024
2024-01-23
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17332
url http://hdl.handle.net/20.500.12105/17332
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412242457362432
score 15,812429

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