Gene free methodology for cell fate dynamics during development
Abstract
Models of cell function that assign a variable to each gene frequently lead to systems of equations with many parameters whose behavior is obscure. Geometric models reduce dynamics to intuitive pictorial elements that provide compact representations for sparse in-vivo data and transparent descriptions of developmental transitions. To illustrate, a geometric model fit to vulval development in C. elegans, implies a phase diagram where cell-fate choices are displayed in a plane defined by EGF and Notch signaling levels. This diagram defines allowable and forbidden cell-fate transitions as EGF or Notch levels change, and explains surprising observations previously attributed to context-dependent action of these signals. The diagram also reveals the existence of special points at which minor changes in signal levels lead to strong epistatic interactions between EGF and Notch. Our model correctly predicts experiments near these points, and suggests specific timed perturbations in signals that can lead to additional unexpected outcomes.
Article and author information
Author details
Funding
National Science Foundation (PHY-1502151)
- Eric D Siggia
National Science Foundation (PHY-1125915)
- Francis Corson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sean R Eddy, Howard Hughes Medical Institute, Harvard University, United States
Version history
- Received: July 25, 2017
- Accepted: December 11, 2017
- Accepted Manuscript published: December 13, 2017 (version 1)
- Version of Record published: January 17, 2018 (version 2)
Copyright
© 2017, Corson & Siggia
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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