Key Points
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Decapentaplegic (DPP) exerts its long-range influence on wing patterning by acting 'directly' at a distance as a gradient morphogen, rather than 'indirectly' as a short-range inducer of other signals.
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Cells in the wing imaginal disc continuously receive and require bone morphogenetic protein (BMP)/DPP signalling input throughout development.
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A biologically active, GFP-tagged form of DPP is currently being used to study different mechanisms of gradient formation.
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The DPP gradient is converted into an inverse transcriptional gradient of Brinker (BRK): the brk gene is negatively controlled by the BMP/DPP transducers Mothers against dpp (MAD) and Medea in conjunction with Schnurri (SHN), a zinc-finger protein. SHN is recruited via the MAD–Medea heterodimer to short silencer elements upstream of the brk coding region, and is essential for brk repression.
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The nested expression boundaries of two well-known DPP target genes (optomoter-blind (omb) and spalt major (salm)) are defined by different levels of BRK (high and low levels, respectively).
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DPP signalling also has a potent growth-promoting role in imaginal disc development.
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Surprisingly, the pattern of cell proliferation in the wing disc is uniform — and it is not highest where DPP levels are maximal.
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The mechanism by which the DPP morphogen gradient controls uniform growth is enigmatic. Several models have been proposed to account for this observation.
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Because cell proliferation seems to occur non-uniformly in the absence of DPP and BRK, the role of the DPP–BRK system seems to correct an inherently uneven proliferation pattern into a uniform pattern of growth.
Abstract
Morphogens have been linked to numerous developmental processes, including organ patterning and the control of organ size. Here we review how different experimental approaches have led to an unprecedented level of molecular knowledge about the patterning role of the Drosophila melanogaster morphogen Decapentaplegic (DPP, the homologue of vertebrate bone morphogenetic protein, or BMP), the first validated secreted morphogen. In addition, we discuss how little is known about the role of the DPP morphogen in the control of organ growth and organ size. Continued efforts to elucidate the role of DPP in D. melanogaster is likely to shed light on this fundamental question in the near future.
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Acknowledgements
We would like to thank A. Weiss for help with the figures and G. Pyrowolakis, A. Weiss, G. Schwank, T. Aegerter-Wilmsen and P. Gallant for discussions and comments and on the manuscript.
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Glossary
- Facilitated diffusion
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The extracellular diffusion of molecules mediated by cell-surface or extracellular matrix proteins.
- Planar transcytosis
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Active transport of a molecule via endocytosis and re-secretion, so that it moves from one cell to a neighbouring cell in a planar fashion within an epithelial sheet.
- Glypican
-
Membrane-associated proteoglycan with a GPI (glycosylphosphatidylinositol) anchor at the C terminus.
- Endocytosis
-
The capture of extracellular molecules via the uptake of membrane vesicles or vacuoles derived from the plasma membrane.
- Photobleach
-
To bleach or destroy the fluorescence of a molecule by intense illumination in a given area of a biological sample. Fluorescence recovery can then be studied as a re-equilibration of the fluorescent signal by molecules from the non-bleached environment.
- Homeodomain-like structure
-
Homeodomains are DNA-binding domains encoded by homeobox proteins. The 60 amino-acid homeodomain folds into a globular domain containing a helix-turn-helix motif, which interacts with residues in the major groove of the target DNA. Additional binding affinity of homeodomains is provided by a flexible N-terminal arm that interacts with the minor groove.
- Organizer
-
A piece of tissue that can induce appropriately organized structures in neighbouring cells.
- Intercalary growth
-
Regeneration that occurs at a tissue boundary between parts that are not normally neighbours.
- Columnar epithelium
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A single-cell layered sheet of elongated epithelial cells arranged on a basement membrane. Cells are joined to their neighbours by specialized junctions such as septate junctions and adherens junctions in flies.
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Affolter, M., Basler, K. The Decapentaplegic morphogen gradient: from pattern formation to growth regulation. Nat Rev Genet 8, 663–674 (2007). https://doi.org/10.1038/nrg2166
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DOI: https://doi.org/10.1038/nrg2166
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