Feedback Loops Shape Cellular Signals in Space and Time

  title={Feedback Loops Shape Cellular Signals in Space and Time},
  author={Onn Brandman and Tobias Meyer},
  pages={390 - 395}
Positive and negative feedback loops are common regulatory elements in biological signaling systems. We discuss core feedback motifs that have distinct roles in shaping signaling responses in space and time. We also discuss approaches to experimentally investigate feedback loops in signaling systems. 
A Regulated Double-Negative Feedback Decodes the Temporal Gradient of Input Stimulation in a Cell Signaling Network
This work has investigated all possible three-node enzymatic networks and identified a network motif that robustly generates a transient or sustained response by acute or gradual stimulation, respectively, and found that a regulated double-negative feedback within the motif is essential for the temporal gradient-sensitive switching.
A controllable gene expression system in liposomes that includes a positive feedback loop.
We introduced a positive feedback loop into a LacI-dependent gene expression system in lipid vesicles, producing a cell-like system that senses and responds to an external signal with a high
Coupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times.
It is shown that a network's bistability range is positively correlated with its maximum open-loop gain and that both quantities depend on the sign of the feedback loops and the type of feedback coupling.
Oscillatory control of signalling molecules.
Regulation of oscillation dynamics in biochemical systems with dual negative feedback loops
  • L. Nguyen
  • Biology
    Journal of The Royal Society Interface
  • 2012
Investigation of the quantitative features of oscillations revealed that coupling negative feedback provides robust tuning of the oscillation dynamics, and it was demonstrated that the mitogen-activated protein kinase (MAPK) cascades also display properties seen in the general nested feedback motifs.
Chemotaxis: A Feedback-Based Computational Model Robustly Predicts Multiple Aspects of Real Cell Behaviour
A simple feedback model of chemotaxis explains how new pseudopods are made and how eukaryotic cells steer toward chemical gradients.
Involvement of the Cytoskeleton in Controlling Leading-Edge Function during Chemotaxis
It is demonstrated that cytoskeletal components required for cortical tension, including MyoII and IQGAP/cortexillins help regulate the level and timing of leading-edge pathways.


Interlinked Fast and Slow Positive Feedback Loops Drive Reliable Cell Decisions
This work investigates why the positive feedback switches that regulate polarization of budding yeast, calcium signaling, Xenopus oocyte maturation, and various other processes use multiple interlinked loops rather than single positive feedback loops.
Feedback control of intercellular signalling in development
This work has highlighted the importance of positive and negative feedback loops in the dynamic regulation of developmental signalling, which can impart precision, robustness and versatility to intercellular signals.
Network motifs: theory and experimental approaches
  • U. Alon
  • Biology
    Nature Reviews Genetics
  • 2007
Network motifs are reviewed, suggesting that they serve as basic building blocks of transcription networks, including signalling and neuronal networks, in diverse organisms from bacteria to humans.
Navigating through models of chemotaxis.
Robust, Tunable Biological Oscillations from Interlinked Positive and Negative Feedback Loops
It is shown that it is generally difficult to adjust a negative feedback oscillator's frequency without compromising its amplitude, whereas with positive-plus-negative feedback, one can achieve a widely tunable frequency and near-constant amplitude.
A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision
The results explain how a group of intrinsically reversible signal transducers can generate an irreversible response at a systems level, and show how a cell fate can be maintained by a self-sustaining pattern of protein kinase activation.
A PtdInsP3- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity
Emergent properties of positive and negative regulatory links between PtdInsP3 and Rho family GTPases may constitute a broadly conserved module for the establishment of cell polarity during eukaryotic chemotaxis.
A synthetic oscillatory network of transcriptional regulators
This work used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli, which periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells.