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Geometry of gene regulatory dynamics

Cornell Affiliated Author(s)

Author

D.A. Rand
A. Raju
M. Sáez
F. Corson
E.D. Siggia

Abstract

Embryonic development leads to the reproducible and ordered appearance of complexity from egg to adult. The successive differentiation of different cell types that elaborate this complexity results from the activity of gene networks and was likened by Waddington to a flow through a landscape in which valleys represent alternative fates. Geometric methods allow the formal representation of such landscapes and codify the types of behaviors that result from systems of differential equations. Results from Smale and coworkers imply that systems encompassing gene network models can be represented as potential gradients with a Riemann metric, justifying the Waddington metaphor. Here, we extend this representation to include parameter dependence and enumerate all three-way cellular decisions realizable by tuning at most two parameters, which can be generalized to include spatial coordinates in a tissue. All diagrams of cell states vs. model parameters are thereby enumerated. We unify a number of standard models for spatial pattern formation by expressing them in potential form (i.e., as topographic elevation). Turing systems appear nonpotential, yet in suitable variables the dynamics are low dimensional and potential. A time-independent embedding recovers the original variables. Lateral inhibition is described by a saddle point with many unstable directions. A model for the patterning of the Drosophila eye appears as relaxation in a bistable potential. Geometric reasoning provides intuitive dynamic models for development that are well adapted to fit time-lapse data. © 2021 National Academy of Sciences. All rights reserved.

Date Published

Journal

Proceedings of the National Academy of Sciences of the United States of America

Volume

118

Issue

38

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85114854863&doi=10.1073%2fpnas.2109729118&partnerID=40&md5=3e281f592b4e4ab8e0eb7ea2a7389684

DOI

10.1073/pnas.2109729118

Research Area

Funding Source

PHY-1748958
R25GM067110
2919.02
FC001051
EP/P019811/1
2013131
ANR16-CE13-0003-02

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