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An ensemble-averaged, cell density-based digital model of zebrafish embryo development derived from light-sheet microscopy data with single-cell resolution

Kobitski, A. Y. 1,2; Otte, J. C. 2; Takamiya, M. 2; Schäfer, B. 1; Mertes, J. 1; Stegmaier, J. 3; Rastegar, S. ORCID iD icon 2; Rindone, F. 4; Hartmann, V. 4; Stotzka, R. ORCID iD icon 4; Garcia, A. 5; Wezel, J. van ORCID iD icon; Mikut, R. ORCID iD icon 3; Strähle, U. 2; Nienhaus, G. U. 1,2
1 Institut für Angewandte Physik (APH), Karlsruher Institut für Technologie (KIT)
2 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)
3 Institut für Angewandte Informatik (IAI), Karlsruher Institut für Technologie (KIT)
4 Institut für Prozessdatenverarbeitung und Elektronik (IPE), Karlsruher Institut für Technologie (KIT)
5 Steinbuch Centre for Computing (SCC), Karlsruher Institut für Technologie (KIT)


A new era in developmental biology has been ushered in by recent advances in the quantitative imaging of all-cell morphogenesis in living organisms. Here we have developed a light-sheet fluorescence microscopy-based framework with single-cell resolution for identification and characterization of subtle phenotypical changes of millimeter-sized organisms. Such a comparative study requires analyses of entire ensembles to be able to distinguish sample-to-sample variations from definitive phenotypical changes. We present a kinetic digital model of zebrafish embryos up to 16h of development. The model is based on the precise overlay and averaging of data taken on multiple individuals and describes the cell density and its migration direction at every point in time. Quantitative metrics for multi-sample comparative studies have been introduced to analyze developmental variations within the ensemble. The digital model may serve as a canvas on which the behavior of cellular subpopulations can be studied. As an example, we have investigated cellular rearrangements during germ layer formation at the onset of gastrulation. A comparison of the one-eyed pinhead (oep) mutant with the digital model of the wild-type embryo reveals its abnormal development at the onset of gastrulation, many hours before changes are obvious to the eye.

Volltext §
DOI: 10.5445/IR/1000045934
DOI: 10.1038/srep08601
Zitationen: 34
Web of Science
Zitationen: 33
Zitationen: 45
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Informatik (IAI)
Institut für Angewandte Physik (APH)
Institut für Nanotechnologie (INT)
Institut für Prozessdatenverarbeitung und Elektronik (IPE)
Institut für Toxikologie und Genetik (ITG)
Steinbuch Centre for Computing (SCC)
Universität Karlsruhe (TH) – Zentrale Einrichtungen (Zentrale Einrichtungen)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2015
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000045934
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Scientific Reports
Verlag Nature Research
Band 5
Heft 8601
Seiten 1-10
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Schlagwörter Light-sheet microscopy, Biological fluorescence
Nachgewiesen in Dimensions
Web of Science
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