Published online 9 October 2008 | Nature | doi:10.1038/news.2008.1162


Zebrafish development tracked cell by cell

Microscopic imaging reconstructs embryo's first day.

embryoFluorescence microscopy can reconstruct a digital zebrafish embryo.P. KELLER/EMBL

A new type of microscope has allowed scientists to map the behaviour and movements of cells during zebrafish (Danio rerio) embryonic development, and create a three-dimensional digital movie of the process.

The team, from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, says that this is the first complete developmental blueprint of a vertebrate. They think that the technique, called digital scanned laser light-sheet fluorescence microscopy (DSLM), could be applied to embryos of other vertebrates such as mice and frogs.

The researchers tracked individual cells making up the zebrafish embryo — an important model organism — with the laser microscope, which scans a sheet of light across the sample in many different directions to build up a three-dimensional picture.

Caught on camera

The embryo was monitored over 24 hours as it grew from a single cell to tens of thousands of cells. Over 400,000 images were created, providing a vast amount of data on cellular positions, movements and divisions. The results of their study are published in Science1.

Jochen Wittbrodt, a member of the EMBL team, says that these observations are "immediately useful both for research in developmental biology as well as in teaching, considering the many movies we provide to illustrate vertebrate embryogenesis. We see many direct applications of our technology: the quantitative study of mutant defects, the analysis of the level of individuality in different embryos of the same species and the establishment of comprehensive databases of organ development and tissue formation, just to name a few."

Crucially, DSLM uses around 5,000–6,000 times less light than in a confocal fluorescence microscope, thus allowing the living embryos to be observed for significantly longer periods of time without damage.

Vertebrate breakthrough

Until now, mapping the embryonic development of vertebrates has been an unfeasibly enormous task. "So far, no study has been published providing cellular-level resolution data for an entire living vertebrate embryo," says co-author Philipp Keller.

There are only two multi-cellular organisms that have been comprehensively reconstructed in this way, he says. One of them is a sea squirt (Ciona intestinalis); the other is the nematode worm (Caenorhabditis elegans), work on which won Sydney Brenner, Robert Horvitz and John Sulston the Nobel Prize in Physiology or Medicine in 2002.

"This technology, and these maps, should give vertebrate embryologists the ability to study development with the detail and subtlety that has long been available for worms," says Armand Leroi, an evolutionary developmental biologist from Imperial College London, UK, who researches the development of C.elegans.

"John Sulston got his Nobel not for sequencing the human genome or unravelling molecular signalling pathways, but for sitting down in front of a microscope and drawing pictures of cells. This is the same thing: just more cells — and no drawings," says Leroi. 

  • References

    1. Keller, P. J., Schmidt, A. D., Wittbrodt, J. & Stelzer, E. H. K. Science doi:10.1126/science.1162493 (2008).
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