Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch

Authors

Lina Meinecke, University of California, Irvine
Praveer P. Sharma, University of California, Irvine
Huijing Du, University of Nebraska - LincolnFollow
Lei Zhang, Peking University
Qing Nie, University of California, IrvineFollow
Thomas F. Schilling, University of California, IrvineFollow

ORCID IDs

0000-0003-0502-7846

0000-0001-9972-2051

0000-0003-1798-8695

Document Type

Article

Date of this Version

2018

Citation

PLoS Comput Biol 14(11): e1006569

Comments

© 2018 Meinecke et al.

Open access

https://doi.org/10.1371/journal.pcbi.1006569

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.