Sonic hedgehog in temporal control of somite formation
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Publication Date: | 2010 |
Other Authors: | , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | https://hdl.handle.net/1822/29569 |
Summary: | Vertebrate embryo somite formation is temporally controlled by the cyclic expression of somitogenesis clock genes in the presomitic mesoderm (PSM). The somitogenesis clock is believed to be an intrinsic property of this tissue, operating independently of embryonic midline structures and the signaling molecules produced therein, namely Sonic hedgehog (Shh). This work revisits the notochord signaling contribution to temporal control of PSM segmentation by assessing the rate and number of somites formed and somitogenesis molecular clock gene expression oscillations upon notochord ablation. The absence of the notochord causes a delay in somite formation, accompanied by an increase in the period of molecular clock oscillations. Shh is the notochord-derived signal responsible for this effect, as these alterations are recapitulated by Shh signaling inhibitors and rescued by an external Shh supply. We have characterized chick smoothened expression pattern and have found that the PSM expresses both patched1 and smoothened Shh signal transducers. Upon notochord ablation, patched1, gli1, and fgf8 are down-regulated, whereas gli2 and gli3 are overexpressed. Strikingly, notochord-deprived PSM segmentation rate recovers over time, concomitant with raldh2 overexpression. Accordingly, exogenous RA supplement rescues notochord ablation effects on somite formation. A model is presented in which Shh and RA pathways converge to inhibit PSM Gli activity, ensuring timely somite formation. Altogether, our data provide evidence that a balance between different pathways ensures the robustness of timely somite formation and that notochord-derived Shh is a component of the molecular network regulating the pace of the somitogenesis clock. |
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Sonic hedgehog in temporal control of somite formationsomitogenesismolecular clocknotochordScience & TechnologyVertebrate embryo somite formation is temporally controlled by the cyclic expression of somitogenesis clock genes in the presomitic mesoderm (PSM). The somitogenesis clock is believed to be an intrinsic property of this tissue, operating independently of embryonic midline structures and the signaling molecules produced therein, namely Sonic hedgehog (Shh). This work revisits the notochord signaling contribution to temporal control of PSM segmentation by assessing the rate and number of somites formed and somitogenesis molecular clock gene expression oscillations upon notochord ablation. The absence of the notochord causes a delay in somite formation, accompanied by an increase in the period of molecular clock oscillations. Shh is the notochord-derived signal responsible for this effect, as these alterations are recapitulated by Shh signaling inhibitors and rescued by an external Shh supply. We have characterized chick smoothened expression pattern and have found that the PSM expresses both patched1 and smoothened Shh signal transducers. Upon notochord ablation, patched1, gli1, and fgf8 are down-regulated, whereas gli2 and gli3 are overexpressed. Strikingly, notochord-deprived PSM segmentation rate recovers over time, concomitant with raldh2 overexpression. Accordingly, exogenous RA supplement rescues notochord ablation effects on somite formation. A model is presented in which Shh and RA pathways converge to inhibit PSM Gli activity, ensuring timely somite formation. Altogether, our data provide evidence that a balance between different pathways ensures the robustness of timely somite formation and that notochord-derived Shh is a component of the molecular network regulating the pace of the somitogenesis clock.We thank R. Moura, C.J. Sheeba, F. Bajanca, and O. Martinho for helpful input regarding this work, and N. Le Dourain and L. Sa de for critical reading of the manuscript. We also wish to acknowledge stimulating insights provided by the Reviewers. T.P.R was supported by Fundacao para a Ciencia e a Tecnologia (FCT), Portugal (SFRH/BD/27796/2006); R.P.A. is funded by a Ciencia2007 Program Contract (Portuguese Government). This work was supported by FCT, Portugal (Projects PTDC/SAU-OBD/099758/2008 and PTDC/SAU-OBD/105111/2008), the EU/FP6-Network of Excellence-"Cells into Organs" and IBB/CBME, LA, FEDER/POCI 2010.Stanford University's Highwire PresUniversidade do MinhoResende, TatianaFerreira, MónicaTeillet, Marie-AiméeTavares, Ana TeresaAndrade, Raquel P.Palmeirim, I.2010-07-202010-07-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/29569eng0027-842410.1073/pnas.100097910720615943http://www.pnas.org/content/107/29/12907info: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:RCAAP2023-07-21T12:27:10ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Sonic hedgehog in temporal control of somite formation |
title |
Sonic hedgehog in temporal control of somite formation |
spellingShingle |
Sonic hedgehog in temporal control of somite formation Resende, Tatiana somitogenesis molecular clock notochord Science & Technology |
title_short |
Sonic hedgehog in temporal control of somite formation |
title_full |
Sonic hedgehog in temporal control of somite formation |
title_fullStr |
Sonic hedgehog in temporal control of somite formation |
title_full_unstemmed |
Sonic hedgehog in temporal control of somite formation |
title_sort |
Sonic hedgehog in temporal control of somite formation |
author |
Resende, Tatiana |
author_facet |
Resende, Tatiana Ferreira, Mónica Teillet, Marie-Aimée Tavares, Ana Teresa Andrade, Raquel P. Palmeirim, I. |
author_role |
author |
author2 |
Ferreira, Mónica Teillet, Marie-Aimée Tavares, Ana Teresa Andrade, Raquel P. Palmeirim, I. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Resende, Tatiana Ferreira, Mónica Teillet, Marie-Aimée Tavares, Ana Teresa Andrade, Raquel P. Palmeirim, I. |
dc.subject.por.fl_str_mv |
somitogenesis molecular clock notochord Science & Technology |
topic |
somitogenesis molecular clock notochord Science & Technology |
description |
Vertebrate embryo somite formation is temporally controlled by the cyclic expression of somitogenesis clock genes in the presomitic mesoderm (PSM). The somitogenesis clock is believed to be an intrinsic property of this tissue, operating independently of embryonic midline structures and the signaling molecules produced therein, namely Sonic hedgehog (Shh). This work revisits the notochord signaling contribution to temporal control of PSM segmentation by assessing the rate and number of somites formed and somitogenesis molecular clock gene expression oscillations upon notochord ablation. The absence of the notochord causes a delay in somite formation, accompanied by an increase in the period of molecular clock oscillations. Shh is the notochord-derived signal responsible for this effect, as these alterations are recapitulated by Shh signaling inhibitors and rescued by an external Shh supply. We have characterized chick smoothened expression pattern and have found that the PSM expresses both patched1 and smoothened Shh signal transducers. Upon notochord ablation, patched1, gli1, and fgf8 are down-regulated, whereas gli2 and gli3 are overexpressed. Strikingly, notochord-deprived PSM segmentation rate recovers over time, concomitant with raldh2 overexpression. Accordingly, exogenous RA supplement rescues notochord ablation effects on somite formation. A model is presented in which Shh and RA pathways converge to inhibit PSM Gli activity, ensuring timely somite formation. Altogether, our data provide evidence that a balance between different pathways ensures the robustness of timely somite formation and that notochord-derived Shh is a component of the molecular network regulating the pace of the somitogenesis clock. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-07-20 2010-07-20T00:00:00Z |
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/1822/29569 |
url |
https://hdl.handle.net/1822/29569 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0027-8424 10.1073/pnas.1000979107 20615943 http://www.pnas.org/content/107/29/12907 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Stanford University's Highwire Pres |
publisher.none.fl_str_mv |
Stanford University's Highwire Pres |
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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 |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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1777303760985391104 |