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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paper:paper_15449173_v10_n7_p11_Schroter2023-06-08T16:21:10Z Topology and dynamics of the zebrafish segmentation clock core circuit 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. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15449173_v10_n7_p11_Schroter 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 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. |
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 |
publishDate |
2012 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15449173_v10_n7_p11_Schroter http://hdl.handle.net/20.500.12110/paper_15449173_v10_n7_p11_Schroter |
_version_ |
1768543438322532352 |