Morphogen transport

Müller, Patrick; Rogers, Katherine W.; Yu, Shuizi Rachel; Brand, Michael; Schier, Alexander F.

doi:10.1242/dev.083519

Cited by 246 publications

(318 citation statements)

References 177 publications

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“…We now use that Contribution of diffusion and advection to ligand transport. Both, in the simple model as given by equation (3) and in the detailed model for the Dpp gradient in the Drosophila wing imaginal disc as given by equations (8,9), diffusion and advection contribute to ligand transport. Supplementary Fig.…”

Section: Nature Communications | Doi: 101038/ncomms6077 Articlementioning

confidence: 99%

“…How morphogens are transported has remained controversial [2][3][4] . The proposed morphogen dispersal models can be divided into two categories: cell-based and diffusive 4 .…”

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confidence: 99%

“…Internalized ligand can then be transported either by transcytosis 5 , a process by which macromolecules are transported across the interior of a cell, or by cytonemes, that is, by specialized filopodia that mediate long-distance signalling during development 6,7 . Diffusion of morphogens, either freely or hindered 3 , is well documented, but the relative contributions of the different transport mechanisms have remained controversial. According to the French Flag model 8 , cells read out the local morphogen concentration and respond when specific concentration thresholds are exceeded (Fig.…”

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confidence: 99%

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Dynamic scaling of morphogen gradients on growing domains

Fried

Iber

2014

Nat Commun

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Developmental mechanisms are highly conserved, yet act in embryos of very different sizes. How scaling is achieved has remained elusive. Here we identify a generally applicable mechanism for dynamic scaling on growing domains and show that it quantitatively agrees with data from the Drosophila wing imaginal disc. We show that for the measured parameter ranges, the Dpp gradient does not reach steady state during Drosophila wing development. We further show that both, pre-steady-state dynamics and advection of cell-bound ligand in a growing tissue can, in principle, enable scaling, even for non-uniform tissue growth. For the parameter values that have been established for the Dpp morphogen in the Drosophila wing imaginal disc, we show that scaling is mainly a result of the pre-steady-state dynamics. Pre-steady-state dynamics are pervasive in morphogen-controlled systems, thus making this a probable general mechanism for dynamic scaling of morphogen gradients in growing developmental systems.

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Section: Nature Communications | Doi: 101038/ncomms6077 Articlementioning

confidence: 99%

“…How morphogens are transported has remained controversial [2][3][4] . The proposed morphogen dispersal models can be divided into two categories: cell-based and diffusive 4 .…”

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confidence: 99%

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confidence: 99%

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Dynamic scaling of morphogen gradients on growing domains

Fried

Iber

2014

Nat Commun

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“…It has been argued that these signals depend on cellular processes, such as secretion of the ligand, interaction of the ligand with cognate signaling receptors, and degradation of the ligand-receptor complex for the termination of signaling. The latter is often mediated by the endocytosis of morphogens (7,8). Cellular parameters governing these processes need to be quantitatively determined to understand the generation and the interpretation of patterning signals, such as Wg.…”

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confidence: 99%

Endocytosis of Wingless via a dynamin-independent pathway is necessary for signaling in Drosophila wing discs

Hemalatha

Prabhakara

Mayor

2016

Proc. Natl. Acad. Sci. U.S.A.

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Endocytosis of ligand-receptor complexes regulates signal transduction during development. In particular, clathrin and dynamin-dependent endocytosis has been well studied in the context of patterning of the Drosophila wing disc, wherein apically secreted Wingless (Wg) encounters its receptor, DFrizzled2 (DFz2), resulting in a distinctive dorso-ventral pattern of signaling outputs. Here, we directly track the endocytosis of Wg and DFz2 in the wing disc and demonstrate that Wg is endocytosed from the apical surface devoid of DFz2 via a dynamin-independent CLIC/GEEC pathway, regulated by Arf1, Garz, and class I PI3K. Subsequently, Wg containing CLIC/GEEC endosomes fuse with DFz2-containing vesicles derived from the clathrin and dynamin-dependent endocytic pathway, which results in a low pH-dependent transfer of Wg to DFz2 within the merged and acidified endosome to initiate Wg signaling. The employment of two distinct endocytic pathways exemplifies a mechanism wherein cells in tissues leverage multiple endocytic pathways to spatially regulate signaling.clathrin and dynamin-independent endocytosis | Wingless signaling | pH of endosome | wing disc development | Garz localization

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“…The formation and shape of a morphogen gradient is influenced by many factors, such as how the morphogen is produced (36,37), how it is degraded (38,39), how it is transported (23,(40)(41)(42)(43), and how it interacts with other system components (44). The original and conceptually simplest morphogen model involves a single morphogen species that diffuses freely, degrades at constant rate, and is produced/injected at one end of the system (23).…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal Analysis of Different Mechanisms for Interpreting Morphogen Gradients

Richards

Saunders

2015

Biophysical Journal

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During development, multicellular organisms must accurately control both temporal and spatial aspects of tissue patterning. This is often achieved using morphogens, signaling molecules that form spatially varying concentrations and so encode positional information. Typical analysis of morphogens assumes that spatial information is decoded in steady state by measuring the value of the morphogen concentration. However, recent experimental work suggests that both pre-steadystate readout and measurement of spatial and temporal derivatives of the morphogen concentration can play important roles in defining boundaries. Here, we undertake a detailed theoretical and numerical study of the accuracy of patterning-both in space and time-in models where readout is provided not by the morphogen concentration but by its spatial and temporal derivatives. In both cases we find that accurate patterning can be achieved, with sometimes even smaller errors than directly reading the morphogen concentration. We further demonstrate that such models provide other potential benefits to the system, such as the ability to switch on and off gene response with a high degree of spatiotemporal accuracy. Finally, we discuss how such derivatives might be calculated biologically and examine these models in relation to Sonic Hedgehog signaling in the vertebrate central nervous system. We show that, when coupled to a downstream transcriptional network, pre-steady-state measurement of the temporal change in the Shh morphogen is a plausible mechanism for determining precise gene boundaries in both space and time.

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Morphogen transport

Cited by 246 publications

References 177 publications

Dynamic scaling of morphogen gradients on growing domains

Dynamic scaling of morphogen gradients on growing domains

Endocytosis of Wingless via a dynamin-independent pathway is necessary for signaling in Drosophila wing discs

Spatiotemporal Analysis of Different Mechanisms for Interpreting Morphogen Gradients

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