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Operating principles of circular toggle polygons

Hati, S and Duddu, AS and Jolly, MK (2021) Operating principles of circular toggle polygons. In: Physical Biology, 18 (4).

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Official URL: https://doi.org/10.1088/1478-3975/abef79


Decoding the dynamics of cellular decision-making and cell differentiation is a central question in cell and developmental biology. A common network motif involved in many cell-fate decisions is a mutually inhibitory feedback loop between two self-activating 'master regulators' A and B, also called as toggle switch. Typically, it can allow for three stable states - (high A, low B), (low A, high B) and (medium A, medium B). A toggle triad - three mutually repressing regulators A, B and C, i.e. three toggle switches arranged circularly (between A and B, between B and C, and between A and C) - can allow for six stable states: three 'single positive' and three 'double positive' ones. However, the operating principles of larger toggle polygons, i.e. toggle switches arranged circularly to form a polygon, remain unclear. Here, we simulate using both discrete and continuous methods the dynamics of different sized toggle polygons. We observed a pattern in their steady state frequency depending on whether the polygon was an even or odd numbered one. The even-numbered toggle polygons result in two dominant states with consecutive components of the network expressing alternating high and low levels. The odd-numbered toggle polygons, on the other hand, enable more number of states, usually twice the number of components with the states that follow 'circular permutation' patterns in their composition. Incorporating self-activations preserved these trends while increasing the frequency of multistability in the corresponding network. Our results offer insights into design principles of circular arrangement of regulatory units involved in cell-fate decision making, and can offer design strategies for synthesizing genetic circuits.

Item Type: Journal Article
Publication: Physical Biology
Publisher: IOP Publishing Ltd
Additional Information: The copyright for this article belongs to the Authors.
Keywords: biological model; cell differentiation; gene regulatory network; genetics; physiology, Cell Differentiation; Gene Regulatory Networks; Models, Biological
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
UG Programme
Date Deposited: 16 May 2023 09:20
Last Modified: 16 May 2023 09:20
URI: https://eprints.iisc.ac.in/id/eprint/81665

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