Systems Biology of the Drosophila Wing
Multiscale and multiphysics particle simulations of wing development
In this project (started 10/2008) we collaborate with biologists using the Drosophila wing as a model uniquely suited for a systems biology approach. The development of the Drososphila wing is regulated at various levels of complexity ranging from gene regulation and molecular signaling, to cell architecture and biomechanical properties of tissues.
We develop a framework within which computational models of development are integrated with data in order to analyze phenomena on multiple spatial and temporal scales. The uniqueness of our approach is characterized by the advanced computational techniques that have been developed in our labs and the embedding of the modeling effort in an experimental environment in order to introduce a systematic development of biologically informed computational methods for data analysis and predictive modeling. The project is conducted as part of the SystemsX initiative, (under the title WingX), in collaboration with University of Zurich, University of Basel, EPF Lausanne and University of Lausanne.
Drosophila wing as a model organ
The fruit fly – Drosophila melanogaster – has been a crucial model organism for the discovery of basic principles in development. Decades of developmental, cell biological, and above all genetic research have provided a detailed understanding of the genetic networks that govern growth and patterning of this organism and specifically of its wing and thus provide a solid foundation for a systems approach.
People: Gerardo Tauriello, Michael Bergdorf, Basil Bayati
People: Ernst Hafen (ETH Zurich, IMSB), Tinri Aegerter (University of Zurich, IMB), Dario Floreano (EPFL, LIS)
Funding: SystemsX
2011
- G. Schwank, G. Tauriello, R. Yagi, E. Kranz, P. Koumoutsakos, and K. Basler, “Antagonistic growth regulation by dpp and fat drives uniform cell proliferation,” Dev. Cell, vol. 20, iss. 1, p. 123–130, 2011.
[BibTeX] [Abstract] [PDF] [DOI]
We use the Dpp morphogen gradient in the Drosophila wing disc as a model to address the fundamental question of how a gradient of a growth factor can produce uniform growth. We first show that proper expression and subcellular localization of components in the Fat tumor-suppressor pathway, which have been argued to depend on Dpp activity differences, are not reliant on the Dpp gradient. We next analyzed cell proliferation in discs with uniformly high Dpp or uniformly low Fat signaling activity and found that these pathways regulate growth in a complementary manner. While the Dpp mediator Brinker inhibits growth in the primordium primarily in the lateral regions, Fat represses growth mostly in the medial region. Together, our results indicate that the activities of both signaling pathways are regulated in a parallel rather than sequential manner and that uniform proliferation is achieved by their complementary action on growth.
@article{schwank2011a, author = {Gerald Schwank and Gerardo Tauriello and Ryohei Yagi and Elizabeth Kranz and Petros Koumoutsakos and Konrad Basler}, doi = {10.1016/j.devcel.2010.11.007}, journal = {{Dev. Cell}}, month = {jan}, number = {1}, pages = {123--130}, publisher = {Elsevier {BV}}, title = {Antagonistic Growth Regulation by Dpp and Fat Drives Uniform Cell Proliferation}, url = {http://www.cse-lab.ethz.ch/wp-content/papercite-data/pdf/schwank2011a.pdf}, volume = {20}, year = {2011} }