Durrieu L, Kirrmaier D, Schneidt T, Kats I, Raghavan S, Hufnagel L, Saunders TE, Knop M. Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis. Mol Syst Biol. 2018 Sep 4;14(9):e8355. doi: 10.15252/msb.20188355.
Abstract:
Embryogenesis relies on instructions provided by spatially organized signaling molecules known as morphogens. Understanding the principles behind morphogen distribution and how cells interpret locally this information remains a major challenge in developmental biology. Here, we introduce morphogen‐age measurements as a novel approach to test models of morphogen gradient formation. Using a tandem fluorescent timer as a protein age sensor, we find a gradient of increasing age of Bicoid along the anterior–posterior axis in the early Drosophila embryo. Quantitative analysis of the protein age distribution across the embryo reveals that the synthesis–diffusion–degradation model is the most likely model underlying Bicoid gradient formation, and rules out other hypotheses for gradient formation. Moreover, we show that the timer can detect transitions in the dynamics associated with syncytial cellularization. Our results provide new insight into Bicoid gradient formation and demonstrate how morphogen‐age information can complement knowledge about movement, abundance, and distribution, which should be widely applicable to other systems.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This work was supported by the European Molecular Biology Laboratory (L.D., T.S., T.E.S., and L.H.). T.E.S. was further supported by the EMBL Interdisciplinary Post doc Programme (EIPOD) under Marie Curie Actions COFUND, support from the Kavli Institute for Theoretical Physics, Santa Barbara, and a Singapore National Research Foundation Fellowship (NRF2012NRF-NRFF001-094). LD was supported from a post doc EcTOP2 fellowship from the CellNetworks cluster of the excellence initiative of the German research council. L.D., M.K., and L.H. acknowledge support by the CellNetworks, University of Heidelberg, Germany, in the context of the EcTop2 project. The authors gratefully acknowledge the data storage service SDS@hd supported by the Ministry of Science, Research and the Arts Baden‐Württemberg (MWK) and the German Research Foundation (DFG) through grant INST 35/1314‐1 FUGG.