skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on July 15, 2026

Title: From genes to patterns: five key dynamical systems concepts to decode developmental regulatory mechanisms
ABSTRACT Developmental biology seeks to unravel the intricate regulatory mechanisms orchestrating the transformation of a single cell into a complex, multicellular organism. Dynamical systems theory provides a powerful quantitative, visual and intuitive framework for understanding this complexity. This Primer examines five core dynamical systems theory concepts and their applications to pattern formation during development: (1) analysis of phase portraits, (2) bistable switches, (3) stochasticity, (4) response to time-dependent signals, and (5) oscillations. We explore how these concepts shed light onto cell fate decision making and provide insights into the dynamic nature of developmental processes driven by signals and gradients, as well as the role of noise in shaping developmental outcomes. Selected examples highlight how integrating dynamical systems with experimental approaches has significantly advanced our understanding of the regulatory logic underlying development across scales, from molecular networks to tissue-level dynamics.  more » « less
Award ID(s):
2222434
PAR ID:
10630825
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Publisher / Repository:
Development
Date Published:
Journal Name:
Development
Volume:
152
Issue:
14
ISSN:
0950-1991
Page Range / eLocation ID:
dev204617
Subject(s) / Keyword(s):
Developmental dynamics Dynamical systems Modelling Signalling Waddington landscape
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Cellular decision making is the process whereby cells choose one developmental pathway from multiple possible ones, either spontaneously or due to environmental stimuli. Examples in various cell types suggest an almost inexhaustible plethora of underlying molecular mechanisms. In general, cellular decisions rely on the gene regulatory network, which integrates external signals to drive cell fate choice. The search for general principles of such a process benefits from appropriate biological model systems that reveal how and why certain gene regulatory mechanisms drive specific cellular decisions according to ecological context and evolutionary outcomes. In this article, we review the historical and ongoing development of the phage lambda lysis–lysogeny decision as a model system to investigate all aspects of cellular decision making. The unique generality, simplicity, and richness of phage lambda decision making render it a constant source ofmathematical modeling–aided inspiration across all of biology. We discuss the origins and progress of quantitative phage lambda modeling from the 1950s until today, as well as its possible future directions. We provide examples of how modeling enabled methods and theory development, leading to new biological insights by revealing gaps in the theory and pinpointing areas requiring further experimental investigation. Overall, we highlight the utility of theoretical approaches both as predictive tools, to forecast the outcome of novel experiments, and as explanatory tools, to elucidate the natural processes underlying experimental data. 
    more » « less
  2. Although the last 30 years have witnessed the mapping of the wiring diagrams of the gene regulatory networks that dictate cell fate and animal body plans, specific understanding building on such network diagrams that shows how DNA regulatory regions control gene expression lags far behind. These networks have yet to yield the predictive power necessary to, for example, calculate how the concentration dynamics of input transcription factors and DNA regulatory sequence prescribes output patterns of gene expression that, in turn, determine body plans themselves. Here, we argue that reaching a predictive understanding of developmental decision-making calls for an interplay between theory and experiment aimed at revealing how the regulation of the processes of the central dogma dictate network connections and how network topology guides cells toward their ultimate developmental fate. To make this possible, it is crucial to break free from the snapshot-based understanding of embryonic development facilitated by fixed-tissue approaches and embrace new technologies that capture the dynamics of developmental decision-making at the single cell level, in living embryos. 
    more » « less
  3. Abstract Recent technical and theoretical advances have generated an explosion in the identification of specialized metabolite pathways. In comparison, our understanding of how these pathways are regulated is relatively lagging. This and the relatively young age of specialized metabolite pathways has partly contributed to a default and common paradigm whereby specialized metabolite regulation is theorized as relatively simple with a few key transcription factors and the compounds are non-regulatory end-products. In contrast, studies into model specialized metabolites, such as glucosinolates, are beginning to identify a new understanding whereby specialized metabolites are highly integrated into the plants’ core metabolic, physiological, and developmental pathways. This model includes a greatly extended compendium of transcription factors controlling the pathway, key transcription factors that co-evolve with the pathway and simultaneously control core metabolic and developmental components, and finally the compounds themselves evolve regulatory connections to integrate into the plants signaling machinery. In this review, these concepts are illustrated using studies in the glucosinolate pathway within the Brassicales. This suggests that the broader community needs to reconsider how they do or do not integrate specialized metabolism into the regulatory network of their study species. 
    more » « less
  4. Abstract The last decade has witnessed a surge of theoretical and computational models to describe the dynamics of complex gene regulatory networks, and how these interactions can give rise to multistable and heterogeneous cell populations. As the use of theoretical modeling to describe genetic and biochemical circuits becomes more widespread, theoreticians with mathematical and physical backgrounds routinely apply concepts from statistical physics, non-linear dynamics, and network theory to biological systems. This review aims at providing a clear overview of the most important methodologies applied in the field while highlighting current and future challenges. It also includes hands-on tutorials to solve and simulate some of the archetypical biological system models used in the field. Furthermore, we provide concrete examples from the existing literature for theoreticians that wish to explore this fast-developing field. Whenever possible, we highlight the similarities and differences between biochemical and regulatory networks and ‘classical’ systems typically studied in non-equilibrium statistical and quantum mechanics. 
    more » « less
  5. ABSTRACT Biphasic lifecycles are widespread among animals, but little is known about how the developmental transition between larvae and adults is regulated. Sea urchins are a unique system for studying this phenomenon because of the stark differences between their bilateral larval and pentaradial adult body plans. Here, we use single-cell RNA sequencing to analyze the development of Heliocidaris erythrogramma (He), a sea urchin species with an accelerated, non-feeding mode of larval development. The sequencing time course extends from embryogenesis to roughly a day before the onset of metamorphosis in He larvae, which is a period that has not been covered by previous datasets. We find that the non-feeding developmental strategy of He is associated with several changes in the specification of larval cell types compared to sea urchins with feeding larvae, such as the loss of a larva-specific skeletal cell population. Furthermore, the development of the larval and adult body plans in sea urchins may utilize largely different sets of regulatory genes. These findings lay the groundwork for extending existing developmental gene regulatory networks to cover additional stages of biphasic lifecycles. 
    more » « less