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, C., Ares, S., Morelli, L.G., Isakova, A., Hens, K., Soroldoni, D., Gajewski, M., Jülicher, F., Maerkl, S.J., Deplancke, B., Oates, A.C.
Formato:	JOUR
Materias:	basic helix loop helix transcription factor homodimer messenger RNA protein antibody transcription factor Her1 transcription factor Her6 transcription factor Her6 antibody transcription factor Her7 unclassified drug her1 protein, zebrafish HER7 protein, zebrafish repressor protein transcription factor zebrafish protein animal experiment animal tissue article controlled study developmental biology embryo embryo development embryo segmentation embryonic structures gene her1 gene her6 gene her7 gene messenger RNA synthesis molecular clock molecular dynamics mutant nonhuman phenotype prediction protein DNA binding protein function protein stability somitogenesis transcription regulation zebra fish animal biological model biological rhythm cytology dimerization enzyme specificity feedback system gene expression regulation genetic transcription genetics metabolism morphogenesis prenatal development promoter region protein analysis protein protein interaction somite two hybrid system Danio rerio Vertebrata Animals Basic Helix-Loop-Helix Transcription Factors Biological Clocks Body Patterning Dimerization Feedback, Physiological Gene Expression Regulation, Developmental Models, Biological Phenotype Promoter Regions, Genetic Protein Interaction Mapping Protein Interaction Maps Protein Stability Repressor Proteins RNA, Messenger Somites Substrate Specificity Transcription Factors Transcription, Genetic Two-Hybrid System Techniques Zebrafish Zebrafish Proteins
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_15449173_v10_n7_p11_Schroter
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_15449173_v10_n7_p11_Schroter
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spelling	todo:paper_15449173_v10_n7_p11_Schroter2023-10-03T16:22:59Z Topology and dynamics of the zebrafish segmentation clock core circuit Schröter, C. Ares, S. Morelli, L.G. Isakova, A. Hens, K. Soroldoni, D. Gajewski, M. Jülicher, F. Maerkl, S.J. Deplancke, B. Oates, A.C. basic helix loop helix transcription factor homodimer messenger RNA protein antibody transcription factor Her1 transcription factor Her6 transcription factor Her6 antibody transcription factor Her7 unclassified drug basic helix loop helix transcription factor her1 protein, zebrafish HER7 protein, zebrafish messenger RNA repressor protein transcription factor zebrafish protein animal experiment animal tissue article controlled study developmental biology embryo embryo development embryo segmentation embryonic structures gene her1 gene her6 gene her7 gene messenger RNA synthesis molecular clock molecular dynamics mutant nonhuman phenotype prediction protein DNA binding protein function protein stability somitogenesis transcription regulation zebra fish animal biological model biological rhythm cytology dimerization enzyme specificity feedback system gene expression regulation genetic transcription genetics metabolism morphogenesis prenatal development promoter region protein analysis protein protein interaction somite two hybrid system zebra fish Danio rerio Vertebrata Animals Basic Helix-Loop-Helix Transcription Factors Biological Clocks Body Patterning Dimerization Feedback, Physiological Gene Expression Regulation, Developmental Models, Biological Phenotype Promoter Regions, Genetic Protein Interaction Mapping Protein Interaction Maps Protein Stability Repressor Proteins RNA, Messenger Somites Substrate Specificity Transcription Factors Transcription, Genetic Two-Hybrid System Techniques Zebrafish Zebrafish Proteins 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15449173_v10_n7_p11_Schroter
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	basic helix loop helix transcription factor homodimer messenger RNA protein antibody transcription factor Her1 transcription factor Her6 transcription factor Her6 antibody transcription factor Her7 unclassified drug basic helix loop helix transcription factor her1 protein, zebrafish HER7 protein, zebrafish messenger RNA repressor protein transcription factor zebrafish protein animal experiment animal tissue article controlled study developmental biology embryo embryo development embryo segmentation embryonic structures gene her1 gene her6 gene her7 gene messenger RNA synthesis molecular clock molecular dynamics mutant nonhuman phenotype prediction protein DNA binding protein function protein stability somitogenesis transcription regulation zebra fish animal biological model biological rhythm cytology dimerization enzyme specificity feedback system gene expression regulation genetic transcription genetics metabolism morphogenesis prenatal development promoter region protein analysis protein protein interaction somite two hybrid system zebra fish Danio rerio Vertebrata Animals Basic Helix-Loop-Helix Transcription Factors Biological Clocks Body Patterning Dimerization Feedback, Physiological Gene Expression Regulation, Developmental Models, Biological Phenotype Promoter Regions, Genetic Protein Interaction Mapping Protein Interaction Maps Protein Stability Repressor Proteins RNA, Messenger Somites Substrate Specificity Transcription Factors Transcription, Genetic Two-Hybrid System Techniques Zebrafish Zebrafish Proteins
spellingShingle	basic helix loop helix transcription factor homodimer messenger RNA protein antibody transcription factor Her1 transcription factor Her6 transcription factor Her6 antibody transcription factor Her7 unclassified drug basic helix loop helix transcription factor her1 protein, zebrafish HER7 protein, zebrafish messenger RNA repressor protein transcription factor zebrafish protein animal experiment animal tissue article controlled study developmental biology embryo embryo development embryo segmentation embryonic structures gene her1 gene her6 gene her7 gene messenger RNA synthesis molecular clock molecular dynamics mutant nonhuman phenotype prediction protein DNA binding protein function protein stability somitogenesis transcription regulation zebra fish animal biological model biological rhythm cytology dimerization enzyme specificity feedback system gene expression regulation genetic transcription genetics metabolism morphogenesis prenatal development promoter region protein analysis protein protein interaction somite two hybrid system zebra fish Danio rerio Vertebrata Animals Basic Helix-Loop-Helix Transcription Factors Biological Clocks Body Patterning Dimerization Feedback, Physiological Gene Expression Regulation, Developmental Models, Biological Phenotype Promoter Regions, Genetic Protein Interaction Mapping Protein Interaction Maps Protein Stability Repressor Proteins RNA, Messenger Somites Substrate Specificity Transcription Factors Transcription, Genetic Two-Hybrid System Techniques Zebrafish Zebrafish Proteins Schröter, C. Ares, S. Morelli, L.G. Isakova, A. Hens, K. Soroldoni, D. Gajewski, M. Jülicher, F. Maerkl, S.J. Deplancke, B. Oates, A.C. Topology and dynamics of the zebrafish segmentation clock core circuit
topic_facet	basic helix loop helix transcription factor homodimer messenger RNA protein antibody transcription factor Her1 transcription factor Her6 transcription factor Her6 antibody transcription factor Her7 unclassified drug basic helix loop helix transcription factor her1 protein, zebrafish HER7 protein, zebrafish messenger RNA repressor protein transcription factor zebrafish protein animal experiment animal tissue article controlled study developmental biology embryo embryo development embryo segmentation embryonic structures gene her1 gene her6 gene her7 gene messenger RNA synthesis molecular clock molecular dynamics mutant nonhuman phenotype prediction protein DNA binding protein function protein stability somitogenesis transcription regulation zebra fish animal biological model biological rhythm cytology dimerization enzyme specificity feedback system gene expression regulation genetic transcription genetics metabolism morphogenesis prenatal development promoter region protein analysis protein protein interaction somite two hybrid system zebra fish Danio rerio Vertebrata Animals Basic Helix-Loop-Helix Transcription Factors Biological Clocks Body Patterning Dimerization Feedback, Physiological Gene Expression Regulation, Developmental Models, Biological Phenotype Promoter Regions, Genetic Protein Interaction Mapping Protein Interaction Maps Protein Stability Repressor Proteins RNA, Messenger Somites Substrate Specificity Transcription Factors Transcription, Genetic Two-Hybrid System Techniques Zebrafish Zebrafish Proteins
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.
format	JOUR
author	Schröter, C. Ares, S. Morelli, L.G. Isakova, A. Hens, K. Soroldoni, D. Gajewski, M. Jülicher, F. Maerkl, S.J. Deplancke, B. Oates, A.C.
author_facet	Schröter, C. Ares, S. Morelli, L.G. Isakova, A. Hens, K. Soroldoni, D. Gajewski, M. Jülicher, F. Maerkl, S.J. Deplancke, B. Oates, A.C.
author_sort	Schröter, C.
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
url	http://hdl.handle.net/20.500.12110/paper_15449173_v10_n7_p11_Schroter
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_version_	1782028679613775872

Topology and dynamics of the zebrafish segmentation clock core circuit

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