Key Points
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Morphogens are secreted signalling molecules that control the patterning and growth of developing organs. How they regulate patterning is well described, but growth control is less well understood.
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The study of the role of the morphogen Decapentaplegic (DPP) in imaginal disc growth will be useful for understanding other morphogenetic growth systems.
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Four models have been proposed to explain growth control of the wing imaginal disc of Drosophila melanogaster by the morphogen DPP: a permissive growth model based on growth factors and mechanical stress; a permissive growth model centred on Brinker (BRK), the transcriptional repressor in the DPP pathway; an instructive growth model based on relative spatial differences in DPP levels between neighbouring cells; and an instructive growth model based on relative temporal changes in cellular DPP levels.
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DPP signalling also interacts with the Fat–Hippo pathway, which regulates organ size, and this interaction may facilitate growth regulation.
Abstract
Morphogens are secreted signalling molecules that control the patterning and growth of developing organs. How morphogens regulate patterning is fairly well understood; however, how they control growth is less clear. Four principal models have been proposed to explain how the morphogenetic protein Decapentaplegic (DPP) controls the growth of the wing imaginal disc in the fly. Recent studies in this model system have provided a wealth of experimental data on growth and DPP gradient properties, as well as on the interactions of DPP with other signalling pathways. These findings have allowed a more precise formulation and evaluation of morphogenetic growth models. The insights into growth control by the DPP gradient will also be useful for understanding other morphogenetic growth systems.
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Acknowledgements
The authors thank A. Genevet for comments on the manuscript. This work was supported by the Max-Planck-Gesellschaft, the Swiss National Science Foundation, grants from the Swiss SystemsX.ch initiative and LipidX-2008/011, and by an ERC advanced investigator grant to M.G.-G.
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Supplementary information S1 (table) | Useful parameters and equations to characterize growth and morphogen gradients. (PDF 343 kb)
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Glossary
- Imaginal disc
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A flat epithelial pouch in the larva that, during metamorphosis in the pupa, will give rise to an adult structure of the fly.
- Amplitude
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The maximum concentration of a protein in the target region. In the case of Decapentaplegic (DPP), amplitude refers to the concentration at the DPP source boundary. Its value depends on DPP production and degradation rates, as well as on the number of DPP-producing cells (the source width) and on the rate of diffusion.
- Decay length
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A measure for the spatial range of a protein gradient (how far it reaches into the tissue): the position at which the concentration of the protein is a fixed fraction of its amplitude (C0/e; in which e is Euler's number). Its value depends on how fast the molecules diffuse and are degraded (less degradation equals a higher decay length).
- Gradient scaling
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If the gradient expands at the same rate as the tissue, it scales with tissue size; the decay length of the gradient is proportional to the width of the tissue.
- Anisotropic tissue growth
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Directionally dependent growth of a tissue: more growth along one axis (for example, horizontal) than another (for example, vertical) in the plane of the epithelium.
- Spatial derivative
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The spatial difference in a quantity (for example, concentration) across one spatial unit (for example, a cell); the spatial derivative is denoted with a prime symbol, for example dC/dx = C′.
- Time derivative
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The rate of change of a quantity (for example, concentration) over time; the time derivative is denoted with a dot symbol, for example dC/dt = Ċ.
- Planar cell polarity
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A mechanism of cellular organization, distinct from apical–basal polarity, by which cells acquire information about their orientation within the tissue in the plane of the epithelium.
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Wartlick, O., Mumcu, P., Jülicher, F. et al. Understanding morphogenetic growth control — lessons from flies. Nat Rev Mol Cell Biol 12, 594–604 (2011). https://doi.org/10.1038/nrm3169
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DOI: https://doi.org/10.1038/nrm3169
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