Scaling of morphogen gradients

Ben‐Zvi, Danny; Shilo, Ben‐Zion; Barkai, Naama

doi:10.1016/j.gde.2011.07.011

Cited by 78 publications

(67 citation statements)

References 40 publications

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“…Thereby, the expander effectively serves as a chemical size reporter. In contrast to earlier works on gradient scaling [12,[15][16][17][18][21][22][23]], this mechanism is fully self-organized. In particular, it does not rely on prepatterned sources or sinks.…”

Section: Discussioncontrasting

confidence: 60%

“…For a given feedback scheme, the stability of fixed points depends on whether the source is fixed [11,15,21] or dynamic as in our case. For example, two mutually suppressing concentration profiles (here: the inhibitor and the expander) would not result in a stable pattern for a fixed source size, but yield a stable scaling pattern in our case, since the expander also effectively expands the source.…”

mentioning

confidence: 98%

“…It has been proposed that the scaling of these profiles is achieved by a dynamic regulation of the morphogen degradation rate via a chemical signal, called the expander, whose level varies with system size [12,[15][16][17][18]. Different possible realizations for such mechanisms have been proposed [11,12,[15][16][17][18][21][22][23]. These mechanisms rely on prepatterned tissues with specified sources or sinks for morphogens or the expander.…”

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confidence: 99%

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Scaling and Regeneration of Self-Organized Patterns

et al. 2015

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Biological patterns generated during development and regeneration often scale with organism size. Some organisms, e.g., flatworms, can regenerate a rescaled body plan from tissue fragments of varying sizes. Inspired by these examples, we introduce a generalization of Turing patterns that is self-organized and self-scaling. A feedback loop involving diffusing expander molecules regulates the reaction rates of a Turing system, thereby adjusting pattern length scales proportional to system size. Our model captures essential features of body plan regeneration in flatworms as observed in experiments.

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Section: Discussioncontrasting

confidence: 60%

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confidence: 98%

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confidence: 99%

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Scaling and Regeneration of Self-Organized Patterns

et al. 2015

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“…For example, by Biophysical Journal 105(4) 1057-1066 addition of autocatalytic enzymatic reactions or by applying mechanical force to the PAAm hydrogel, the platform can be used to experimentally verify current hypotheses on gradient scaling (21,54) or assess the importance of mechanochemical feedback mechanisms (55). Looking beyond the in vitro study of biochemical networks, we also envisage the importance of ultrasensitivity in materials science, where recent efforts have shown the possibility of engineering autonomous materials capable of mechanical synchronization by coupling of diffusion and chemomechanical feedback loops (56)(57)(58)(59).…”

Section: Discussionmentioning

confidence: 99%

Ultrasensitivity by Molecular Titration in Spatially Propagating Enzymatic Reactions

Semenov

Markvoort

Gevers

et al. 2013

Biophysical Journal

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Delineating design principles of biological systems by reconstitution of purified components offers a platform to gauge the influence of critical physicochemical parameters on minimal biological systems of reduced complexity. Here we unravel the effect of strong reversible inhibitors on the spatiotemporal propagation of enzymatic reactions in a confined environment in vitro. We use micropatterned, enzyme-laden agarose gels which are stamped on polyacrylamide films containing immobilized substrates and reversible inhibitors. Quantitative fluorescence imaging combined with detailed numerical simulations of the reaction-diffusion process reveal that a shallow gradient of enzyme is converted into a steep product gradient by addition of strong inhibitors, consistent with a mathematical model of molecular titration. The results confirm that ultrasensitive and threshold effects at the molecular level can convert a graded input signal to a steep spatial response at macroscopic length scales.

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“…In contrast, in Drosophila, the Chordin homolog Sog, is produced on the ventral side of the embryo, where it binds and inhibits diffusion of the Bmp homolog Dpp from the dorsal side of the embryo. The complex is then transported back to the dorsal side of the embryo for degradation (Ben-Zvi et al, 2011;Ben-Zvi et al, 2008;O'Connor et al, 2006;Plouhinec et al, 2011). Other known regulators, such as the metalloproteinase Tolloid, can bind and digest Chd.…”

Section: Introductionmentioning

confidence: 99%

Coordinate involvement of Nodal-dependent inhibition and Wnt-dependent activation in the maintenance of organizer-specific bmp2b in zebrafish

Xue

Xing²,

Zhang³

et al. 2016

Int. J. Dev. Biol.

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A vertebrate signaling center, known in zebrafish as the organizer, is essential for axis patterning and formation and is regulated by multiple cell signaling pathways, including Wnt, Nodal, and Bmp. Organizer-specific Bmp2b plays important roles in the maintenance of the Bmp activity gradient and dorsal-ventral patterning. However, it is unknown how transcription of bmp2b in the organizer is regulated. In this study, we generated a bmp2b transgenic line Tsg(-2.272bmp2b:gfp) that reproduced organizer-specific bmp2b expression. Dissection analysis revealed that a 0.273-kb minimal promoter was indispensable for bmp2b expression in the dorsal organizer. Reporter assays showed that organizer-specific bmp2b is negatively regulated by the Nodal signal and positively regulated by the Wnt signal in both embryos and cell lines. Promoter analysis and chromatin-immunoprecipitation (ChIP) indicated that one consensus Smad-binding element (SBE) (CAGAC) and one Lef/Tcf-binding element (LBE) (AGATAA) were present in the 0.273-kb promoter, and could be directly bound by Smad2 and b-catenin proteins. Together, these results suggest that maintenance of organizer-specific bmp2b expression involves opposite and concerted regulation by Nodal and Wnt signaling.

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Scaling of morphogen gradients

Cited by 78 publications

References 40 publications

Scaling and Regeneration of Self-Organized Patterns

Scaling and Regeneration of Self-Organized Patterns

Ultrasensitivity by Molecular Titration in Spatially Propagating Enzymatic Reactions

Coordinate involvement of Nodal-dependent inhibition and Wnt-dependent activation in the maintenance of organizer-specific bmp2b in zebrafish

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