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Investigating synchronization processes during somitogenesis using microfluidics

Applicant Sonnen Katharina
Number 146958
Funding scheme Fellowships for prospective researchers
Research institution Developmental Biology Unit European Molecular Biology Laboratory EMBL
Institution of higher education Institution abroad - IACH
Main discipline Embryology, Developmental Biology
Start/End 01.02.2013 - 30.06.2013
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Keywords (5)

somitogenesis; mouse; signalling oscillations; cell proliferation; kinematic waves

Lay Summary (German)

Lead
Untersuchung der Somitenbildung während der EmbryonalentwicklungBei der Entwicklung eines Organismus müssen die Vermehrung von Zellen und deren Umwandlung in spezifische Zellarten genau reguliert werden. Ein wichtiger Prozess in der frühen Embryonalentwicklung ist die Bildung von sogenannten Somiten, Vorläufern von Wirbeln.
Lay summary

Somiten entstehen nacheinander vom Kopf in Richtung Schwanz. Zeitlich wird dieser Prozess durch das Zusammenspiel von drei verschiedenen Signalwegen reguliert. Bis heute ist jedoch nicht genau verstanden, wie dabei benachbarte Zellen miteinander kommunizieren. Außerdem ist noch unbekannt, wie die Zellvermehrung während der Entstehung von Somiten kontrolliert wird.

Daher möchte ich diese Fragen addressieren und die Signalwege untersuchen, die den Prozess der Somitenentstehung in Mäusen regulieren. Dabei sollen diese Zellen aus Mäusen isoliert und im Labor kultiviert werden. Um die einzelnen Signalwege sichtbar zu machen, werden bestimmte Bausteine der einzelnen Signalwege mit Fluoreszenz-Farbstoffen markiert. Die Folgen der Manipulation der einzelnen Signalwege (Hemmung oder Aktivierung) sollen dann mikroskopisch in lebenden Zellen analysiert werden. Dieser dynamische, quantitative, so noch nicht angewandte Ansatz ist ideal, um den dynamischen Prozess der Somitenbildung zu untersuchen.

Zusammenfassend soll mit diesem Projekt unser Verständnis vom Ablauf der Somitenbildung in Wirbeltieren verbessert werden.

Direct link to Lay Summary Last update: 10.12.2012

Responsible applicant and co-applicants

Publications

Publication
Dynamic signal encoding—From cells to organisms
Sonnen Katharina F. Aulehla Alexander (2014), Dynamic signal encoding—From cells to organisms, in Seminars in Cell & Developmental Biology, 34, 91-98.

Collaboration

Group / person Country
Types of collaboration
Paul Francois, McGill University Canada (North America)
- in-depth/constructive exchanges on approaches, methods or results
Christoph Merten, EMBL Heidelberg Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Wnt seminar Heidelberg Individual talk Function of phase shift between Wnt- and Notch-signalling oscillations during mouse somitogenesis 12.09.2016 Heidelberg, Germany Sonnen Katharina;
Microfluidics 2016 Poster Study of dynamic signalling during mouse somitogenesis using microfluidics 24.07.2016 Heidelberg, Germany Sonnen Katharina;
EMBL Lab Day 2016 Talk given at a conference Phase shift between Wnt and Notch signalling oscillations is critical for mouse somitogenesis 22.07.2016 Heidelberg, Germany Sonnen Katharina;
Cellular signalling and cancer therapy Poster Study of dynamics signalling signalling during mouse somitogenesis using microfluidics 27.05.2016 Dubrovnik, Croatia Sonnen Katharina;
Biological oscillators: Design, mechanism and function Poster Investigating signalling dynamics governing mouse somitogenesis by microfluidics 12.11.2015 Heidelberg, Germany Sonnen Katharina;
Rhythms in complex networks: from theory to experiment Poster study of dynamic signalling during mouse somitogenesis by microfluidics 01.09.2014 Kopenhagen, Denmark Sonnen Katharina;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Lab Day EMBL 2013 International 2013

Abstract

Development is a highly ordered process in which both cell duplication and differentiation have to be tightly regulated. A key event in vertebrate embryonic development is somitogenesis, the formation of somites, vertebrae precursors, in the presomitic mesoderm (PSM). The consecutive generation of somites is regulated in time by a molecular oscillator. Key components of this so-called segmentation clock are FGF, Notch and Wnt signalling, which have oscillatory activities, generating travelling waves slightly phase-shifted in a posterior-anterior direction. How the waves develop and whether cell-cell communication is involved remains unknown. Furthermore, somitogenesis also requires the ordered multiplication of cells. Interestingly, Wnt, FGF and Notch induce cell cycle entry in other systems. Conversely, the cell cycle also affects Wnt signalling. However, cell cycle regulation during somitogenesis and its relation to the segmentation clock in mice have not been addressed directly so far.Here, I intend to use a mouse model system of segment formation in combination with realtime imaging and microfluidics-based manipulation to study signalling oscillations during mesoderm segmentation in mice. To this end, I will make use of an in vitro cultivation system of segment formation. Cells from fluorescence reporter mice are explanted from mouse PSM and grown in culture to allow the analysis of oscillations of fluorescently tagged molecules by live cell microscopy. Additionally, I will apply microfluidics to manipulate the cells during the analysis by realtime imaging, which constitutes an unprecedented approach to this fundamental developmental process.Using this dynamic, quantitative approach I will address two research questions: firstly, what role the cell cycle plays in the context of the segmentation clock and secondly, how cells within the PSM communicate with each other to generate spatially and temporally synchronized oscillations.Thus, this project aims at improving our mechanistic understanding of somitogenesis in vertebrates.
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