Biology subjects

Garcia-Guillen, J.

Publications and source records attributed to Garcia-Guillen, J..

3 recordsLinked to original sources

bioRxiv2026

Temporal-to-spatial patterning of embryonic structures can involve active transformation of temporal information rather than direct mapping

How spatial patterns arise during embryonic development is classically explained by the French Flag model, in which cells acquire positional identities by interpreting morphogen concentration thresholds. However, in many developmental systems, spatial patterns instead emerge progressively through temporal programs of gene expression that are transformed into spatial organization. For example, in the short-germ insect Tribolium castaneum, both periodic pair-rule gene expressions that generate body segments and non-periodic gap gene expressions that establish regional identities arise sequentially at the posterior and propagate anteriorly in waves across the developing embryo. Understanding how such temporal gene expression programs are translated into spatial patterns remains a major challenge. To address this problem, we developed a sequential multiplexed imaging strategy based on hybridization chain reaction (HCR), enabling visualization of up to ten anterior-posterior (AP) patterning genes within the same Tribolium embryo. By combining this approach with intronic-exonic labeling, we established a framework to infer gene expression dynamics and propagatory behavior during AP patterning. Using this framework, we show that gap gene expression domains remain dynamic and continue to propagate during tissue elongation, indicating that spatial patterns are actively remodeled throughout development. We then directly compared temporal gene activation at the posterior with the resulting spatial organization of pair-rule and gap genes. Surprisingly, while primary pair-rule genes preserve their temporal phase relationships in space, gap genes do not. Instead, the relative positioning of gap gene domains progressively changes as they move anteriorly, indicating that the final spatial organization of gap genes is actively reshaped during propagation rather than being directly inherited from the initial temporal sequence. The continued propagatory behavior of gap gene domains suggests that such reshaping could arise through differential propagation dynamics between genes and/or through progressive reconfiguration of underlying gene regulatory interactions during pattern formation. Together, these findings reveal that temporal-to-spatial patterning can involve active transformation of temporal information rather than a simple mapping from time into space.

developmental biology↗

bioRxiv2025

Gene network switching provides a mechanistic basis for time-to-space translation in insect embryonic patterning

The French Flag model has long served as the prevailing framework for explaining how morphogen gradients generate spatial domains during embryonic development. More recently, however, evidence has shown that many tissues instead establish patterns by translating the sequential activation of genes (organized into genetic cascades) into spatial domains. This translation is thought to occur through modulation of the speed or timing of cascade progression, but the mechanisms underlying such temporal control remain unclear. Two models have been proposed: the general kinetic modulation model, in which morphogens influence global kinetic factors such as transcription and decay rates, and the gene regulatory network (GRN) switching model, in which morphogens reconfigure regulatory interactions so that genes initially function within a genetic cascade driving sequential activation, but are later integrated into a stabilizing network that locks their expression into mutually reinforcing domains. This transition is hypothesized to occur through a shift from a dynamic GRN (a genetic cascade that drives sequential activations) to a static GRN (a stabilizing network that maintains gene expression domains). Using gap genes in Tribolium castaneum as a model, we combined HCR in situ hybridization, parental RNA interference, and computational modeling to test these hypotheses. We show that gap genes initially act in a genetic cascade producing sequential activations, followed by a morphogen-dependent reconfiguration that stabilizes spatial domains. In particular, we identify the Mlpt-Svb complex as a key stabilizing factor that maintains svb expression anteriorly after its initial activation in the posterior. Computational simulations reproduce experimental phenotypes and support GRN switching as the underlying mechanism. Together, these findings demonstrate how morphogen-driven rewiring of network interactions converts temporal cascades into stable spatial patterns, providing a mechanistic basis for robust anterior- posterior patterning in insect embryos and beyond.

developmental biology↗

bioRxiv2024

From Genes to Patterns: A Framework for Modeling the Emergence of Embryonic Development from Transcriptional Regulation

Understanding embryonic patterning, the process by which groups of cells are partitioned into distinct identities defined by gene expression, is a central challenge in developmental biology. This complex phenomenon is driven by precise spatial and temporal regulation of gene expression across many cells, resulting in the emergence of highly organized tissue structures. While similar emergent behavior is well understood in other fields, such as statistical mechanics, the regulation of gene expression in development remains less clear, particularly regarding how molecular-level gene interactions lead to the large-scale patterns observed in embryos. In this study, we present a modeling framework that bridges the gap between molecular gene regulation and tissue-level embryonic patterning. Beginning with basic chemical reaction models of transcription at the single-gene level, we progress to model gene regulatory networks (GRNs) that mediate specific cellular functions. We then introduce phenomenological models of pattern formation, including the French Flag and Temporal Patterning/Speed Regulation models, and integrate them with molecular/GRN realizations. To facilitate understanding and application of our models, we accompany our mathematical framework with computer simulations, providing intuitive and simple code for each model. A key feature of our framework is the explicit articulation of underlying assumptions at each level of the model, from transcriptional regulation to tissue patterning. By making these assumptions clear, we provide a foundation for future experimental and theoretical work to critically examine and challenge them, thereby improving the accuracy and relevance of gene regulatory models in developmental biology. As a case study, we explore how different strategies for integrating enhancer activity affect the robustness and evolvability of gene expression patterns in embryonic development. Our simulations suggest that a two-step regulation strategy, enhancer activation followed by competitive integration at the promoter, ensures more standardized integration of new enhancers into developmental GRNs, highlighting the adaptability of eukaryotic transcription. These findings provide new insights into the transcriptional mechanisms underlying embryonic patterning, offering a framework for future experimental and theoretical investigations.

developmental biology↗