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Topology and Dynamics of the Zebrafish Segmentation Clock Core Circuit

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 biochemi...

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Autores principales: Schröter, Christian, Ares, Saúl, Morelli, Luis G., Isakova, Alina, Hens, Korneel, Soroldoni, Daniele, Gajewski, Martin, Jülicher, Frank, Maerkl, Sebastian J., Deplancke, Bart, Oates, Andrew C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404119/
https://www.ncbi.nlm.nih.gov/pubmed/22911291
http://dx.doi.org/10.1371/journal.pbio.1001364
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author Schröter, Christian
Ares, Saúl
Morelli, Luis G.
Isakova, Alina
Hens, Korneel
Soroldoni, Daniele
Gajewski, Martin
Jülicher, Frank
Maerkl, Sebastian J.
Deplancke, Bart
Oates, Andrew C.
author_facet Schröter, Christian
Ares, Saúl
Morelli, Luis G.
Isakova, Alina
Hens, Korneel
Soroldoni, Daniele
Gajewski, Martin
Jülicher, Frank
Maerkl, Sebastian J.
Deplancke, Bart
Oates, Andrew C.
author_sort Schröter, Christian
collection PubMed
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.
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spelling pubmed-34041192012-07-30 Topology and Dynamics of the Zebrafish Segmentation Clock Core Circuit Schröter, Christian Ares, Saúl Morelli, Luis G. Isakova, Alina Hens, Korneel Soroldoni, Daniele Gajewski, Martin Jülicher, Frank Maerkl, Sebastian J. Deplancke, Bart Oates, Andrew C. PLoS Biol Research Article 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. Public Library of Science 2012-07-24 /pmc/articles/PMC3404119/ /pubmed/22911291 http://dx.doi.org/10.1371/journal.pbio.1001364 Text en Schröter et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Schröter, Christian
Ares, Saúl
Morelli, Luis G.
Isakova, Alina
Hens, Korneel
Soroldoni, Daniele
Gajewski, Martin
Jülicher, Frank
Maerkl, Sebastian J.
Deplancke, Bart
Oates, Andrew C.
Topology and Dynamics of the Zebrafish Segmentation Clock Core Circuit
title 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_short Topology and Dynamics of the Zebrafish Segmentation Clock Core Circuit
title_sort topology and dynamics of the zebrafish segmentation clock core circuit
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404119/
https://www.ncbi.nlm.nih.gov/pubmed/22911291
http://dx.doi.org/10.1371/journal.pbio.1001364
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