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Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis

Lucia Durrieu, Daniel Kirrmaier, Tatjana Schneidt, Ilia Kats, Sarada Raghavan, Michael Knop, Timothy E Saunders, Lars Hufnagel
doi: https://doi.org/10.1101/280834
Lucia Durrieu
1Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
2European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.
6Current address: Instituto Leloir, Av. Patricias Argentinas 435, C1405BWE Ciudad de Buenos Aires, Argentina; Departamento de Fisiología, Biología Molecular, y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires,Buenos Aires, Argentina.
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Daniel Kirrmaier
1Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
3Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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Tatjana Schneidt
2European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.
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Ilia Kats
1Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
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Sarada Raghavan
1Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
7Current address: p53 Laboratory, A*STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648
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Michael Knop
1Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
3Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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  • For correspondence: m.knop@zmbh.uni-heidelberg.de dbsste@nus.edu.sg hufnagel@embl.de
Timothy E Saunders
2European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.
4Mechanobiology Institute and Department of Biological Sciences, National University of Singapore 117411, Singapore
5Institute of Molecular and Cell Biology, A*Star, Biopolis 138673, Singapore
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  • For correspondence: m.knop@zmbh.uni-heidelberg.de dbsste@nus.edu.sg hufnagel@embl.de
Lars Hufnagel
2European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.
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  • For correspondence: m.knop@zmbh.uni-heidelberg.de dbsste@nus.edu.sg hufnagel@embl.de
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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 retrieve key parameters in morphogen dynamics. Using a tandem fluorescent timer (tFT) as a protein-age sensor we find a gradient of increasing age of Bicoid (Bcd) along the anterior-posterior (AP) axis in the early Drosophila embryo. Quantitative analysis retrieves parameter that are most consistent with the synthesis-diffusion-degradation (SDD) model underlying Bcd-gradient formation, and rule out some 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 Bcd gradient formation, and demonstrate how morphogen age-information can complement knowledge about movement, abundance and distribution, which should be widely applicable for other systems.

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Posted March 13, 2018.
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Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis
Lucia Durrieu, Daniel Kirrmaier, Tatjana Schneidt, Ilia Kats, Sarada Raghavan, Michael Knop, Timothy E Saunders, Lars Hufnagel
bioRxiv 280834; doi: https://doi.org/10.1101/280834
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Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis
Lucia Durrieu, Daniel Kirrmaier, Tatjana Schneidt, Ilia Kats, Sarada Raghavan, Michael Knop, Timothy E Saunders, Lars Hufnagel
bioRxiv 280834; doi: https://doi.org/10.1101/280834

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