Zimmerman group ::

Genetic and transgenic analysis of Xenopus tropicalis

• The frog Xenopus tropicalis
• Gynogenetic screens for chemically-induced mutations
  • ENU phenotype database
• High throughput reverse genetics/TILLING
• Binary transgenic systems
• X. tropicalis protocols

Research overview :: studying the genetics of vertebrate development with frog eggs

Our group is broadly interested in understanding how a single cell (the fertilised egg) becomes a developing vertebrate embryo, with organs such as the heart, brain, and sensory structures putting themselves together and functioning properly in the correct locations.

Since all vertebrates use a similar set of genes to accomplish most developmental functions, we choose to study frog embryos, all of whose developmental processes from fertilisation onward occur externally. Our main approach is to use genetics to learn how individual genes function in development, by studying embryos which are missing working versions of those genes. For this reason, we are working on a frog from equatorial West Africa, Xenopus tropicalis, which has a relatively simple gene structure compared to other well-studied frogs and fish.

Assigning functions to genes identified in large-scale EST and genomic sequencing is fundamental to understanding vertebrate development, health and disease. Gain–of-function strategies, such as mRNA injection and transgenic misexpression, identify activities of which gene products are capable, but for which they are not necessarily responsible during development. Loss-of-function strategies, such as analysis of null mutants and morpholino antisense 'knockdown', identify roles for which particular genes are required.

We are developing the amphibian Xenopus tropicalis as a model in which vertebrate gene function can be approached with combinations of loss-of-function, gain-of-function, and embryological techniques. Another member of the genus, X. laevis, has been a highly productive model system in cell and developmental biology due to the ease of molecular and surgical manipulations of its embryos, but its complex pseudotetraploid genome and relatively long generation time have precluded genetic approaches. Another important vertebrate genetic model system, the zebrafish, also possesses a complex genome as a result of an ancestral genome duplication.

With the potential to combine classical embryological approaches with genetic and transgenic tools in a single model system, X. tropicalis is uniquely positioned to contribute to the functional interpretation of the vertebrate genome.

[Supported by the Medical Research Council and NIH grant 1 RO1 HD4 2276-01]

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[Page last updated 11 Dec 2006]

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