A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos

Background: The segregation of the hypoblast and the emergence of the pluripotent epiblast mark the final stages of blastocyst formation in mammalian embryos. In bovine embryos the formation of the hypoblast has been partially studied, and evidence shows that MEK signalling plays a limited role in t...

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Autores principales: Canizo, Jésica Romina, Ynsaurralde Rivolta, Amanda Eugenia, Vazquez Echegaray, Camila, Suvá, Mariana, Alberio, Virgilia, Aller Atucha, Juan Florencio, Guberman, Alejandra, Salamone, Daniel Felipe, Alberio, Ricardo, Alberio, Ramiro
Formato: info:ar-repo/semantics/artículo
Lenguaje:Inglés
Publicado: BioMed Central 2019
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12123/6009
https://bmcdevbiol.biomedcentral.com/articles/10.1186/s12861-019-0193-9
https://doi.org/10.1186/s12861-019-0193-9
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author Canizo, Jésica Romina
Ynsaurralde Rivolta, Amanda Eugenia
Vazquez Echegaray, Camila
Suvá, Mariana
Alberio, Virgilia
Aller Atucha, Juan Florencio
Guberman, Alejandra
Salamone, Daniel Felipe
Alberio, Ricardo
Alberio, Ramiro
author_browse Alberio, Ramiro
Alberio, Ricardo
Alberio, Virgilia
Aller Atucha, Juan Florencio
Canizo, Jésica Romina
Guberman, Alejandra
Salamone, Daniel Felipe
Suvá, Mariana
Vazquez Echegaray, Camila
Ynsaurralde Rivolta, Amanda Eugenia
author_facet Canizo, Jésica Romina
Ynsaurralde Rivolta, Amanda Eugenia
Vazquez Echegaray, Camila
Suvá, Mariana
Alberio, Virgilia
Aller Atucha, Juan Florencio
Guberman, Alejandra
Salamone, Daniel Felipe
Alberio, Ricardo
Alberio, Ramiro
author_sort Canizo, Jésica Romina
collection INTA Digital
description Background: The segregation of the hypoblast and the emergence of the pluripotent epiblast mark the final stages of blastocyst formation in mammalian embryos. In bovine embryos the formation of the hypoblast has been partially studied, and evidence shows that MEK signalling plays a limited role in the segregation of this lineage. Here we explored the role of different signalling pathways during lineage segregation in the bovine embryo using immunofluorescence analysis of NANOG and SOX17 as readouts of epiblast and hypoblast, respectively. Results We show that SOX17 starts to be expressed in 16–32-cell stage embryos, whereas NANOG is first detected from 8-cell stage. SOX17 is first co-expressed with NANOG, but these markers become mutually exclusive by the late blastocyst stage. By assessing the expression kinetics of NANOG/SOX17 we show that inhibition of MEK signalling can eliminate SOX17 expression in bovine blastocysts, without altering NANOG expression. Modulation of WNT, PKC and LIF did not affect NANOG expression in the epiblast when used in combination with the ERK inhibitor. Conclusions This study shows that SOX17 can be used as a reliable early marker of hypoblast in the bovine, and based on its expression profile we show that the hypoblast segregates in day 7 blastocysts. Furthermore, SOX17 expression is abolished using 1 μM of PD0325901, without affecting the NANOG population in the epiblast. Modulation of WNT, PKC and LIF are not sufficient to support enhanced NANOG expression in the epiblast when combined with ERK inhibitor, indicating that additional signalling pathways should be examined to determine their potential roles in epiblast expansion.
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institution Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina)
language Inglés
publishDate 2019
publishDateRange 2019
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publisher BioMed Central
publisherStr BioMed Central
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spelling INTA60092024-06-07T11:34:13Z A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos Canizo, Jésica Romina Ynsaurralde Rivolta, Amanda Eugenia Vazquez Echegaray, Camila Suvá, Mariana Alberio, Virgilia Aller Atucha, Juan Florencio Guberman, Alejandra Salamone, Daniel Felipe Alberio, Ricardo Alberio, Ramiro Ganado Bovino Embriones Animales Segregación Linaje Inmunofluorescencia Cattle Animal Embryos Segregation Lineage Immunofluorescence Background: The segregation of the hypoblast and the emergence of the pluripotent epiblast mark the final stages of blastocyst formation in mammalian embryos. In bovine embryos the formation of the hypoblast has been partially studied, and evidence shows that MEK signalling plays a limited role in the segregation of this lineage. Here we explored the role of different signalling pathways during lineage segregation in the bovine embryo using immunofluorescence analysis of NANOG and SOX17 as readouts of epiblast and hypoblast, respectively. Results We show that SOX17 starts to be expressed in 16–32-cell stage embryos, whereas NANOG is first detected from 8-cell stage. SOX17 is first co-expressed with NANOG, but these markers become mutually exclusive by the late blastocyst stage. By assessing the expression kinetics of NANOG/SOX17 we show that inhibition of MEK signalling can eliminate SOX17 expression in bovine blastocysts, without altering NANOG expression. Modulation of WNT, PKC and LIF did not affect NANOG expression in the epiblast when used in combination with the ERK inhibitor. Conclusions This study shows that SOX17 can be used as a reliable early marker of hypoblast in the bovine, and based on its expression profile we show that the hypoblast segregates in day 7 blastocysts. Furthermore, SOX17 expression is abolished using 1 μM of PD0325901, without affecting the NANOG population in the epiblast. Modulation of WNT, PKC and LIF are not sufficient to support enhanced NANOG expression in the epiblast when combined with ERK inhibitor, indicating that additional signalling pathways should be examined to determine their potential roles in epiblast expansion. EEA Balcarce Fil: Canizo, Jesica Romina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil: Ynsaurralde Rivolta, Amada Eugenia. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mercedes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vazquez Echegaray, Camila. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Suvá, Mariana. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Alberio, Virgilia. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Aller, Juan Florencio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Fil: Guberman, Alejandra S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fil: Salamone, Daniel.F. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Fil: Alberio, Ricardo H. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Fil: Alberio, Ramiro. University of Nottingham. School of Biosciences; Reino Unido 2019-09-30T11:08:27Z 2019-09-30T11:08:27Z 2019-07-04 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/6009 https://bmcdevbiol.biomedcentral.com/articles/10.1186/s12861-019-0193-9 1471-213X https://doi.org/10.1186/s12861-019-0193-9 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf BioMed Central BMC Developmental Biology 19 : 13 (2019)
spellingShingle Ganado Bovino
Embriones Animales
Segregación
Linaje
Inmunofluorescencia
Cattle
Animal Embryos
Segregation
Lineage
Immunofluorescence
Canizo, Jésica Romina
Ynsaurralde Rivolta, Amanda Eugenia
Vazquez Echegaray, Camila
Suvá, Mariana
Alberio, Virgilia
Aller Atucha, Juan Florencio
Guberman, Alejandra
Salamone, Daniel Felipe
Alberio, Ricardo
Alberio, Ramiro
A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos
title A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos
title_full A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos
title_fullStr A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos
title_full_unstemmed A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos
title_short A dose-dependent response to MEK inhibition determines hypoblast fate in bovine embryos
title_sort dose dependent response to mek inhibition determines hypoblast fate in bovine embryos
topic Ganado Bovino
Embriones Animales
Segregación
Linaje
Inmunofluorescencia
Cattle
Animal Embryos
Segregation
Lineage
Immunofluorescence
url http://hdl.handle.net/20.500.12123/6009
https://bmcdevbiol.biomedcentral.com/articles/10.1186/s12861-019-0193-9
https://doi.org/10.1186/s12861-019-0193-9
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