Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/142544 |
Resumo: | The establishment of separated pulmonary and systemic circulation in vertebrates, via the cardiac outflow tract (OFT) septation is a sensitive developmental process accounting for 10% of all congenital anomalies. Neural Crest Cells (NCC) colonising the heart condensate along the primitive endocardial tube and force its scission into two tubes. Here, we show that NCC aggregation progressively decreases along the OFT distal-proximal axis following a BMP signalling gradient. Dullard, a nuclear phosphatase, tunes the BMP gradient amplitude and prevents NCC premature condensation. Dullard maintains transcriptional programs providing NCC with mesenchymal traits. It attenuates the expression of the aggregation factor Sema3c and conversely promotes that of the epithelial-mesenchymal transition driver Twist1. Altogether, Dullard-mediated fine-tuning of BMP signalling ensures the timed and progressive zipper-like closure of the OFT by the NCC and prevents the formation of an heart carrying the four congenital abnormalities defining the tetralogy of Fallot. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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spelling |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septationThe establishment of separated pulmonary and systemic circulation in vertebrates, via the cardiac outflow tract (OFT) septation is a sensitive developmental process accounting for 10% of all congenital anomalies. Neural Crest Cells (NCC) colonising the heart condensate along the primitive endocardial tube and force its scission into two tubes. Here, we show that NCC aggregation progressively decreases along the OFT distal-proximal axis following a BMP signalling gradient. Dullard, a nuclear phosphatase, tunes the BMP gradient amplitude and prevents NCC premature condensation. Dullard maintains transcriptional programs providing NCC with mesenchymal traits. It attenuates the expression of the aggregation factor Sema3c and conversely promotes that of the epithelial-mesenchymal transition driver Twist1. Altogether, Dullard-mediated fine-tuning of BMP signalling ensures the timed and progressive zipper-like closure of the OFT by the NCC and prevents the formation of an heart carrying the four congenital abnormalities defining the tetralogy of Fallot.eLife Sciences Publications20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/142544eng2050-084X10.7554/eLife.50325Darrigrand, JFValente, MComai, GMartinez, PPetit, MNishinakamura, ROsório, DSRenault, GMarchiol, CRibes, VCadot, Binfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T15:49:34Zoai:repositorio-aberto.up.pt:10216/142544Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:33:09.732546Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation |
title |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation |
spellingShingle |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation Darrigrand, JF |
title_short |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation |
title_full |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation |
title_fullStr |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation |
title_full_unstemmed |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation |
title_sort |
Dullard-mediated smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation |
author |
Darrigrand, JF |
author_facet |
Darrigrand, JF Valente, M Comai, G Martinez, P Petit, M Nishinakamura, R Osório, DS Renault, G Marchiol, C Ribes, V Cadot, B |
author_role |
author |
author2 |
Valente, M Comai, G Martinez, P Petit, M Nishinakamura, R Osório, DS Renault, G Marchiol, C Ribes, V Cadot, B |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Darrigrand, JF Valente, M Comai, G Martinez, P Petit, M Nishinakamura, R Osório, DS Renault, G Marchiol, C Ribes, V Cadot, B |
description |
The establishment of separated pulmonary and systemic circulation in vertebrates, via the cardiac outflow tract (OFT) septation is a sensitive developmental process accounting for 10% of all congenital anomalies. Neural Crest Cells (NCC) colonising the heart condensate along the primitive endocardial tube and force its scission into two tubes. Here, we show that NCC aggregation progressively decreases along the OFT distal-proximal axis following a BMP signalling gradient. Dullard, a nuclear phosphatase, tunes the BMP gradient amplitude and prevents NCC premature condensation. Dullard maintains transcriptional programs providing NCC with mesenchymal traits. It attenuates the expression of the aggregation factor Sema3c and conversely promotes that of the epithelial-mesenchymal transition driver Twist1. Altogether, Dullard-mediated fine-tuning of BMP signalling ensures the timed and progressive zipper-like closure of the OFT by the NCC and prevents the formation of an heart carrying the four congenital abnormalities defining the tetralogy of Fallot. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/142544 |
url |
https://hdl.handle.net/10216/142544 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2050-084X 10.7554/eLife.50325 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
eLife Sciences Publications |
publisher.none.fl_str_mv |
eLife Sciences Publications |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799136239985623040 |