Integrating force-sensing and signaling pathways in a model for the regulation of wing imaginal disc size
pmid: 22833127
Integrating force-sensing and signaling pathways in a model for the regulation of wing imaginal disc size
The regulation of organ size constitutes a major unsolved question in developmental biology. The wing imaginal disc of Drosophila serves as a widely used model system to study this question. Several mechanisms have been proposed to have an impact on final size, but they are either contradicted by experimental data or they cannot explain a number of key experimental observations and may thus be missing crucial elements. We have modeled a regulatory network that integrates the experimentally confirmed molecular interactions underlying other available models. Furthermore, the network includes hypothetical interactions between mechanical forces and specific growth regulators, leading to a size regulation mechanism that conceptually combines elements of existing models, and can be understood in terms of a compression gradient model. According to this model, compression increases in the center of the disc during growth. Growth stops once compression levels in the disc center reach a certain threshold and the compression gradient drops below a certain level in the rest of the disc. Our model can account for growth termination as well as for the paradoxical observation that growth occurs uniformly in the presence of a growth factor gradient and non-uniformly in the presence of a uniform growth factor distribution. Furthermore, it can account for other experimental observations that argue either in favor or against other models. The model also makes specific predictions about the distribution of cell shape and size in the developing disc, which we were able to confirm experimentally.
- University of Bern Switzerland
- University of Zurich Switzerland
Organ Size, Models, Biological, 10124 Institute of Molecular Life Sciences, SX13 Plant Growth, Biomechanical Phenomena, 1309 Developmental Biology, SX00 SystemsX.ch, Imaginal Discs, SX15 WingX, 1312 Molecular Biology, Pressure, 570 Life sciences; biology, Animals, Wings, Animal, Computer Simulation, Drosophila, Cell Shape, Signal Transduction
Organ Size, Models, Biological, 10124 Institute of Molecular Life Sciences, SX13 Plant Growth, Biomechanical Phenomena, 1309 Developmental Biology, SX00 SystemsX.ch, Imaginal Discs, SX15 WingX, 1312 Molecular Biology, Pressure, 570 Life sciences; biology, Animals, Wings, Animal, Computer Simulation, Drosophila, Cell Shape, Signal Transduction
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