Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.7/645 |
Resumo: | Formation of the vertebrate axial skeleton requires coordinated Hox gene activity. Hox group 6 genes are involved in the formation of the thoracic area owing to their unique rib-promoting properties. Here we show that the linker region (LR) connecting the homeodomain and the hexapeptide is essential for Hoxb6 rib-promoting activity in mice. The LR-defective Hoxb6 protein was still able to bind a target enhancer together with Pax3, producing a dominant-negative effect, indicating that the LR brings additional regulatory factors to target DNA elements. We also found an unexpected association between Hoxb6 and segmentation in the paraxial mesoderm. In particular, Hoxb6 can disturb somitogenesis and anterior-posterior somite patterning by dysregulation of Lfng expression. Interestingly, this interaction occurred differently in thoracic versus more caudal embryonic areas, indicating functional differences in somitogenesis before and after the trunk-to-tail transition. Our results suggest the requirement of precisely regulated Hoxb6 expression for proper segmentation at tailbud stages. |
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Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activityHox genesVertebrate patterningAxial skeletonGene regulationMouseFormation of the vertebrate axial skeleton requires coordinated Hox gene activity. Hox group 6 genes are involved in the formation of the thoracic area owing to their unique rib-promoting properties. Here we show that the linker region (LR) connecting the homeodomain and the hexapeptide is essential for Hoxb6 rib-promoting activity in mice. The LR-defective Hoxb6 protein was still able to bind a target enhancer together with Pax3, producing a dominant-negative effect, indicating that the LR brings additional regulatory factors to target DNA elements. We also found an unexpected association between Hoxb6 and segmentation in the paraxial mesoderm. In particular, Hoxb6 can disturb somitogenesis and anterior-posterior somite patterning by dysregulation of Lfng expression. Interestingly, this interaction occurred differently in thoracic versus more caudal embryonic areas, indicating functional differences in somitogenesis before and after the trunk-to-tail transition. Our results suggest the requirement of precisely regulated Hoxb6 expression for proper segmentation at tailbud stages.Fundação para a Ciência e a Tecnologia grant: (PTDC/SAU-BID/110640/2009); FCT postdoctoral fellowship: (SFRH/BPD/89500/2012).Company of BiologistsARCACasaca, AnaNóvoa, AnaMallo, Moisés2016-06-14T15:06:40Z2016-02-012016-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.7/645engHoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity Ana Casaca, Ana Nóvoa, Moisés Mallo Development 2016 143: 437-448; doi: 10.1242/dev.13307410.1242/dev.133074info: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:RCAAP2022-11-29T14:35:02Zoai:arca.igc.gulbenkian.pt:10400.7/645Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:53.347924Repositório 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 |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity |
title |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity |
spellingShingle |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity Casaca, Ana Hox genes Vertebrate patterning Axial skeleton Gene regulation Mouse |
title_short |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity |
title_full |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity |
title_fullStr |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity |
title_full_unstemmed |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity |
title_sort |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity |
author |
Casaca, Ana |
author_facet |
Casaca, Ana Nóvoa, Ana Mallo, Moisés |
author_role |
author |
author2 |
Nóvoa, Ana Mallo, Moisés |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Casaca, Ana Nóvoa, Ana Mallo, Moisés |
dc.subject.por.fl_str_mv |
Hox genes Vertebrate patterning Axial skeleton Gene regulation Mouse |
topic |
Hox genes Vertebrate patterning Axial skeleton Gene regulation Mouse |
description |
Formation of the vertebrate axial skeleton requires coordinated Hox gene activity. Hox group 6 genes are involved in the formation of the thoracic area owing to their unique rib-promoting properties. Here we show that the linker region (LR) connecting the homeodomain and the hexapeptide is essential for Hoxb6 rib-promoting activity in mice. The LR-defective Hoxb6 protein was still able to bind a target enhancer together with Pax3, producing a dominant-negative effect, indicating that the LR brings additional regulatory factors to target DNA elements. We also found an unexpected association between Hoxb6 and segmentation in the paraxial mesoderm. In particular, Hoxb6 can disturb somitogenesis and anterior-posterior somite patterning by dysregulation of Lfng expression. Interestingly, this interaction occurred differently in thoracic versus more caudal embryonic areas, indicating functional differences in somitogenesis before and after the trunk-to-tail transition. Our results suggest the requirement of precisely regulated Hoxb6 expression for proper segmentation at tailbud stages. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-06-14T15:06:40Z 2016-02-01 2016-02-01T00:00:00Z |
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 |
http://hdl.handle.net/10400.7/645 |
url |
http://hdl.handle.net/10400.7/645 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity Ana Casaca, Ana Nóvoa, Moisés Mallo Development 2016 143: 437-448; doi: 10.1242/dev.133074 10.1242/dev.133074 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Company of Biologists |
publisher.none.fl_str_mv |
Company of Biologists |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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1799130573832192000 |