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: Christian Schröter, Saúl Ares, Luis G Morelli, Alina Isakova, Korneel Hens, Daniele Soroldoni, Martin Gajewski, Frank Jülicher, Sebastian J Maerkl, Bart Deplancke, Andrew C Oates
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/877d839941f6424693533ce27c29264d
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spelling oai:doaj.org-article:877d839941f6424693533ce27c29264d2021-11-18T05:36:35ZTopology and dynamics of the zebrafish segmentation clock core circuit.1544-91731545-788510.1371/journal.pbio.1001364https://doaj.org/article/877d839941f6424693533ce27c29264d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22911291/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885During 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.Christian SchröterSaúl AresLuis G MorelliAlina IsakovaKorneel HensDaniele SoroldoniMartin GajewskiFrank JülicherSebastian J MaerklBart DeplanckeAndrew C OatesPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 10, Iss 7, p e1001364 (2012)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Christian Schröter
Saúl Ares
Luis G Morelli
Alina Isakova
Korneel Hens
Daniele Soroldoni
Martin Gajewski
Frank Jülicher
Sebastian J Maerkl
Bart Deplancke
Andrew C Oates
Topology and dynamics of the zebrafish segmentation clock core circuit.
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.
format article
author Christian Schröter
Saúl Ares
Luis G Morelli
Alina Isakova
Korneel Hens
Daniele Soroldoni
Martin Gajewski
Frank Jülicher
Sebastian J Maerkl
Bart Deplancke
Andrew C Oates
author_facet Christian Schröter
Saúl Ares
Luis G Morelli
Alina Isakova
Korneel Hens
Daniele Soroldoni
Martin Gajewski
Frank Jülicher
Sebastian J Maerkl
Bart Deplancke
Andrew C Oates
author_sort Christian Schröter
title Topology and dynamics of the zebrafish segmentation clock core circuit.
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.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/877d839941f6424693533ce27c29264d
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