PUBLICATION
Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch
- Authors
- Meinecke, L., Sharma, P.P., Du, H., Zhang, L., Nie, Q., Schilling, T.F.
- ID
- ZDB-PUB-181128-4
- Date
- 2018
- Source
- PLoS Computational Biology 14: e1006569 (Journal)
- Registered Authors
- Schilling, Tom
- Keywords
- none
- MeSH Terms
-
- Animals
- Body Patterning/physiology*
- Bone Morphogenetic Proteins/metabolism*
- Branchial Region
- Cell Adhesion
- Computer Simulation
- Gene Expression Regulation
- Gene Expression Regulation, Developmental*
- Green Fluorescent Proteins/metabolism
- Mandible/embryology*
- Mandible/physiology*
- Reproducibility of Results
- Signal Transduction
- Stochastic Processes
- Transgenes
- Zebrafish
- Zebrafish Proteins/genetics
- PubMed
- 30481168 Full text @ PLoS Comput. Biol.
Citation
Meinecke, L., Sharma, P.P., Du, H., Zhang, L., Nie, Q., Schilling, T.F. (2018) Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch. PLoS Computational Biology. 14:e1006569.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping