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Position-dependent feedback drives scaling and robustness of morphogen gradients.

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Title: Position-dependent feedback drives scaling and robustness of morphogen gradients.
Authors: Mosby, Lewis Scott1,2,3, Hadjivasiliou, Zena1,2,3 zena.hadjivasiliou@ucl.ac.uk
Source: Proceedings of the National Academy of Sciences of the United States of America. 5/26/2026, Vol. 123 Issue 21, p1-10. 10p.
Subjects: Pattern formation (Biology), Feedback control systems, Cellular signal transduction, Biological evolution, Perturbation theory
Abstract: Developmental patterning is remarkably robust to intrinsic and extrinsic variation. Morphogen gradients are a key mechanism driving patterning, and themselves often scale with the size of developing tissues and exhibit robustness to other perturbations. Recent data indicate that expander molecules, thought to drive morphogen scaling through expansion-repression (ER) feedback, have concentration profiles that are position dependent.This challengesthe currently accepted ER mechanism thatrequires uniform expander concentrations and position independent feedback. To reconcile these observations, we introduce an ER motif that supports morphogen scaling with both uniform and position-dependent expander concentrations. We quantify scaling as a function of position, and demonstrate thatthe spatial profiles ofscaling and robustness to perturbationsin morphogen production are highly correlated.In contrast to uniform expander concentrations that can confer high levels of scaling and robustness at a single position, position-dependent expander concentrations can enhance both scaling and robustness throughout the entire target tissue. We explore trade-offs associated with the dynamic range of the expander concentration, revealing that it can be varied to tune the locations where morphogen gradients confer scaling, robustness, and precision simultaneously. These findings offer insight into how developmental systems balance competing demands to achieve reproducible patterning despite biological variability. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
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Abstract:Developmental patterning is remarkably robust to intrinsic and extrinsic variation. Morphogen gradients are a key mechanism driving patterning, and themselves often scale with the size of developing tissues and exhibit robustness to other perturbations. Recent data indicate that expander molecules, thought to drive morphogen scaling through expansion-repression (ER) feedback, have concentration profiles that are position dependent.This challengesthe currently accepted ER mechanism thatrequires uniform expander concentrations and position independent feedback. To reconcile these observations, we introduce an ER motif that supports morphogen scaling with both uniform and position-dependent expander concentrations. We quantify scaling as a function of position, and demonstrate thatthe spatial profiles ofscaling and robustness to perturbationsin morphogen production are highly correlated.In contrast to uniform expander concentrations that can confer high levels of scaling and robustness at a single position, position-dependent expander concentrations can enhance both scaling and robustness throughout the entire target tissue. We explore trade-offs associated with the dynamic range of the expander concentration, revealing that it can be varied to tune the locations where morphogen gradients confer scaling, robustness, and precision simultaneously. These findings offer insight into how developmental systems balance competing demands to achieve reproducible patterning despite biological variability. [ABSTRACT FROM AUTHOR]
ISSN:00278424
DOI:10.1073/pnas.2521182123