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Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch
How does pattern formation occur accurately when confronted with tissue growth and stochastic fluctuations (noise) in gene expression? Dorso-ventral (D-V) patterning of the mandibular arch specifies upper versus lower jaw skeletal elements through a combination of Bone morphogenetic protein (Bmp), E...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258504/ https://www.ncbi.nlm.nih.gov/pubmed/30481168 http://dx.doi.org/10.1371/journal.pcbi.1006569 |
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author | Meinecke, Lina Sharma, Praveer P. Du, Huijing Zhang, Lei Nie, Qing Schilling, Thomas F. |
author_facet | Meinecke, Lina Sharma, Praveer P. Du, Huijing Zhang, Lei Nie, Qing Schilling, Thomas F. |
author_sort | Meinecke, Lina |
collection | PubMed |
description | How does pattern formation occur accurately when confronted with tissue growth and stochastic fluctuations (noise) in gene expression? Dorso-ventral (D-V) patterning of the mandibular arch specifies upper versus lower jaw skeletal elements through a combination of Bone morphogenetic protein (Bmp), Endothelin-1 (Edn1), and Notch signaling, and this system is highly robust. We combine NanoString experiments of early D-V gene expression with live imaging of arch development in zebrafish to construct a computational model of the D-V mandibular patterning network. The model recapitulates published genetic perturbations in arch development. Patterning is most sensitive to changes in Bmp signaling, and the temporal order of gene expression modulates the response of the patterning network to noise. Thus, our integrated systems biology approach reveals non-intuitive features of the complex signaling system crucial for craniofacial development, including novel insights into roles of gene expression timing and stochasticity in signaling and gene regulation. |
format | Online Article Text |
id | pubmed-6258504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-62585042018-12-06 Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch Meinecke, Lina Sharma, Praveer P. Du, Huijing Zhang, Lei Nie, Qing Schilling, Thomas F. PLoS Comput Biol Research Article How does pattern formation occur accurately when confronted with tissue growth and stochastic fluctuations (noise) in gene expression? Dorso-ventral (D-V) patterning of the mandibular arch specifies upper versus lower jaw skeletal elements through a combination of Bone morphogenetic protein (Bmp), Endothelin-1 (Edn1), and Notch signaling, and this system is highly robust. We combine NanoString experiments of early D-V gene expression with live imaging of arch development in zebrafish to construct a computational model of the D-V mandibular patterning network. The model recapitulates published genetic perturbations in arch development. Patterning is most sensitive to changes in Bmp signaling, and the temporal order of gene expression modulates the response of the patterning network to noise. Thus, our integrated systems biology approach reveals non-intuitive features of the complex signaling system crucial for craniofacial development, including novel insights into roles of gene expression timing and stochasticity in signaling and gene regulation. Public Library of Science 2018-11-27 /pmc/articles/PMC6258504/ /pubmed/30481168 http://dx.doi.org/10.1371/journal.pcbi.1006569 Text en © 2018 Meinecke 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Meinecke, Lina Sharma, Praveer P. Du, Huijing Zhang, Lei Nie, Qing Schilling, Thomas F. Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch |
title | Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch |
title_full | Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch |
title_fullStr | Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch |
title_full_unstemmed | Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch |
title_short | Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch |
title_sort | modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258504/ https://www.ncbi.nlm.nih.gov/pubmed/30481168 http://dx.doi.org/10.1371/journal.pcbi.1006569 |
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