Topology and dynamics of the zebrafish segmentation clock core circuit

Autores
Schroter, Christian; Ares, Saúl; Morelli, Luis Guillermo; Isakova, Alina; Hens, Korneel; Soroldoni, Daniele; Gajewski, Martin; Jülicher, Frank; Maerkl, Sebastian J.; Deplancke, Bart; Oates, Andrew C.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
During vertebrate embryogenesis, the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock. We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation of the network's topology and precise measurements of somitogenesis dynamics in novel genetic mutants. We show that the core pace-making circuit consists of two distinct negative feedback loops, one with Her1 homodimers and the other with Her7:Hes6 heterodimers, operating in parallel. To explain the observed single and double mutant phenotypes of her1, her7, and hes6 mutant embryos in our dynamic model, we postulate that the availability and effective stability of the dimers with DNA binding activity is controlled in a "dimer cloud" that contains all possible dimeric combinations between the three factors. This feature of our model predicts that Hes6 protein levels should oscillate despite constant hes6 mRNA production, which we confirm experimentally using novel Hes6 antibodies. The control of the circuit's dynamics by a population of dimers with and without DNA binding activity is a new principle for the segmentation clock and may be relevant to other biological clocks and transcriptional regulatory networks. © 2012 Schröter et al.
Fil: Schroter, Christian. University of Cambridge; Estados Unidos
Fil: Ares, Saúl. Max Planck Institute For The Physics Of Complex Systems; Alemania
Fil: Morelli, Luis Guillermo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Fil: Isakova, Alina. Ecole Polytechnique Federale de Lausanne; Francia
Fil: Hens, Korneel. Ecole Polytechnique Federale de Lausanne; Francia
Fil: Soroldoni, Daniele. Max Planck Institute Of Molecular Cell Biology And Genetics; Alemania
Fil: Gajewski, Martin. Universitat zu Köln; Alemania
Fil: Jülicher, Frank. Max Planck Institute For The Physics Of Complex Systems; Alemania
Fil: Maerkl, Sebastian J.. Ecole Polytechnique Federale de Lausanne; Francia
Fil: Deplancke, Bart. Ecole Polytechnique Federale de Lausanne; Francia
Fil: Oates, Andrew C.. Max Planck Institute Of Molecular Cell Biology And Genetics; Alemania
Materia
segmentation clock
core circuit
genetic network
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/56741
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/56741
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Topology and dynamics of the zebrafish segmentation clock core circuitSchroter, ChristianAres, SaúlMorelli, Luis GuillermoIsakova, AlinaHens, KorneelSoroldoni, DanieleGajewski, MartinJülicher, FrankMaerkl, Sebastian J.Deplancke, BartOates, Andrew C.segmentation clockcore circuitgenetic networkhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1During vertebrate embryogenesis, the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock. We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation of the network's topology and precise measurements of somitogenesis dynamics in novel genetic mutants. We show that the core pace-making circuit consists of two distinct negative feedback loops, one with Her1 homodimers and the other with Her7:Hes6 heterodimers, operating in parallel. To explain the observed single and double mutant phenotypes of her1, her7, and hes6 mutant embryos in our dynamic model, we postulate that the availability and effective stability of the dimers with DNA binding activity is controlled in a "dimer cloud" that contains all possible dimeric combinations between the three factors. This feature of our model predicts that Hes6 protein levels should oscillate despite constant hes6 mRNA production, which we confirm experimentally using novel Hes6 antibodies. The control of the circuit's dynamics by a population of dimers with and without DNA binding activity is a new principle for the segmentation clock and may be relevant to other biological clocks and transcriptional regulatory networks. © 2012 Schröter et al.Fil: Schroter, Christian. University of Cambridge; Estados UnidosFil: Ares, Saúl. Max Planck Institute For The Physics Of Complex Systems; AlemaniaFil: Morelli, Luis Guillermo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Isakova, Alina. Ecole Polytechnique Federale de Lausanne; FranciaFil: Hens, Korneel. Ecole Polytechnique Federale de Lausanne; FranciaFil: Soroldoni, Daniele. Max Planck Institute Of Molecular Cell Biology And Genetics; AlemaniaFil: Gajewski, Martin. Universitat zu Köln; AlemaniaFil: Jülicher, Frank. Max Planck Institute For The Physics Of Complex Systems; AlemaniaFil: Maerkl, Sebastian J.. Ecole Polytechnique Federale de Lausanne; FranciaFil: Deplancke, Bart. Ecole Polytechnique Federale de Lausanne; FranciaFil: Oates, Andrew C.. Max Planck Institute Of Molecular Cell Biology And Genetics; AlemaniaPublic Library of Science2012-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/56741Schroter, Christian; Ares, Saúl; Morelli, Luis Guillermo; Isakova, Alina; Hens, Korneel; et al.; Topology and dynamics of the zebrafish segmentation clock core circuit; Public Library of Science; PLoS Biology; 10; 7; 7-2012; 1001364-10013641544-9173CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001364info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pbio.1001364info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:02:14Zoai:ri.conicet.gov.ar:11336/56741instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:02:14.412CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Topology and dynamics of the zebrafish segmentation clock core circuit
title Topology and dynamics of the zebrafish segmentation clock core circuit
spellingShingle Topology and dynamics of the zebrafish segmentation clock core circuit
Schroter, Christian
segmentation clock
core circuit
genetic network
title_short Topology and dynamics of the zebrafish segmentation clock core circuit
title_full Topology and dynamics of the zebrafish segmentation clock core circuit
title_fullStr Topology and dynamics of the zebrafish segmentation clock core circuit
title_full_unstemmed Topology and dynamics of the zebrafish segmentation clock core circuit
title_sort Topology and dynamics of the zebrafish segmentation clock core circuit
dc.creator.none.fl_str_mv Schroter, Christian
Ares, Saúl
Morelli, Luis Guillermo
Isakova, Alina
Hens, Korneel
Soroldoni, Daniele
Gajewski, Martin
Jülicher, Frank
Maerkl, Sebastian J.
Deplancke, Bart
Oates, Andrew C.
author Schroter, Christian
author_facet Schroter, Christian
Ares, Saúl
Morelli, Luis Guillermo
Isakova, Alina
Hens, Korneel
Soroldoni, Daniele
Gajewski, Martin
Jülicher, Frank
Maerkl, Sebastian J.
Deplancke, Bart
Oates, Andrew C.
author_role author
author2 Ares, Saúl
Morelli, Luis Guillermo
Isakova, Alina
Hens, Korneel
Soroldoni, Daniele
Gajewski, Martin
Jülicher, Frank
Maerkl, Sebastian J.
Deplancke, Bart
Oates, Andrew C.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv segmentation clock
core circuit
genetic network
topic segmentation clock
core circuit
genetic network
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv During vertebrate embryogenesis, the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock. We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation of the network's topology and precise measurements of somitogenesis dynamics in novel genetic mutants. We show that the core pace-making circuit consists of two distinct negative feedback loops, one with Her1 homodimers and the other with Her7:Hes6 heterodimers, operating in parallel. To explain the observed single and double mutant phenotypes of her1, her7, and hes6 mutant embryos in our dynamic model, we postulate that the availability and effective stability of the dimers with DNA binding activity is controlled in a "dimer cloud" that contains all possible dimeric combinations between the three factors. This feature of our model predicts that Hes6 protein levels should oscillate despite constant hes6 mRNA production, which we confirm experimentally using novel Hes6 antibodies. The control of the circuit's dynamics by a population of dimers with and without DNA binding activity is a new principle for the segmentation clock and may be relevant to other biological clocks and transcriptional regulatory networks. © 2012 Schröter et al.
Fil: Schroter, Christian. University of Cambridge; Estados Unidos
Fil: Ares, Saúl. Max Planck Institute For The Physics Of Complex Systems; Alemania
Fil: Morelli, Luis Guillermo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Fil: Isakova, Alina. Ecole Polytechnique Federale de Lausanne; Francia
Fil: Hens, Korneel. Ecole Polytechnique Federale de Lausanne; Francia
Fil: Soroldoni, Daniele. Max Planck Institute Of Molecular Cell Biology And Genetics; Alemania
Fil: Gajewski, Martin. Universitat zu Köln; Alemania
Fil: Jülicher, Frank. Max Planck Institute For The Physics Of Complex Systems; Alemania
Fil: Maerkl, Sebastian J.. Ecole Polytechnique Federale de Lausanne; Francia
Fil: Deplancke, Bart. Ecole Polytechnique Federale de Lausanne; Francia
Fil: Oates, Andrew C.. Max Planck Institute Of Molecular Cell Biology And Genetics; Alemania
description During vertebrate embryogenesis, the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock. We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation of the network's topology and precise measurements of somitogenesis dynamics in novel genetic mutants. We show that the core pace-making circuit consists of two distinct negative feedback loops, one with Her1 homodimers and the other with Her7:Hes6 heterodimers, operating in parallel. To explain the observed single and double mutant phenotypes of her1, her7, and hes6 mutant embryos in our dynamic model, we postulate that the availability and effective stability of the dimers with DNA binding activity is controlled in a "dimer cloud" that contains all possible dimeric combinations between the three factors. This feature of our model predicts that Hes6 protein levels should oscillate despite constant hes6 mRNA production, which we confirm experimentally using novel Hes6 antibodies. The control of the circuit's dynamics by a population of dimers with and without DNA binding activity is a new principle for the segmentation clock and may be relevant to other biological clocks and transcriptional regulatory networks. © 2012 Schröter et al.
publishDate 2012
dc.date.none.fl_str_mv 2012-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/56741
Schroter, Christian; Ares, Saúl; Morelli, Luis Guillermo; Isakova, Alina; Hens, Korneel; et al.; Topology and dynamics of the zebrafish segmentation clock core circuit; Public Library of Science; PLoS Biology; 10; 7; 7-2012; 1001364-1001364
1544-9173
CONICET Digital
CONICET
url http://hdl.handle.net/11336/56741
identifier_str_mv Schroter, Christian; Ares, Saúl; Morelli, Luis Guillermo; Isakova, Alina; Hens, Korneel; et al.; Topology and dynamics of the zebrafish segmentation clock core circuit; Public Library of Science; PLoS Biology; 10; 7; 7-2012; 1001364-1001364
1544-9173
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001364
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pbio.1001364
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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