The African clawed frog

As a model organism Xenopus laevis has a number of key benefits, from the ease in which they can be kept, to their abundant supply of large, robust eggs that can be simply manipulated in the lab.

The early years

The history of experimental embryology using amphibians stretches back to the 1880s, when German embryologist Wilhelm Roux removed one cell of a two-cell frog embryo. Unviable half-embryos resulted, left or right side only, indicating that the two original cells had different fates.

German scientists were the undeniable world experts in embryology at this time.

At this time, German scientists were undeniably the world experts in embryology, the science of the development from fertilisation to embryo. During these early years they were using newts, salamanders, frogs and sea urchins to understand early development.

However, embryological research before the Second World War was hampered by a lack of eggs, which had to be collected in the wild. Researchers would have to rush to find the eggs of frogs or newts during the spawning season, and then work quickly to do their experiments. They would then spend the rest of the year working out what they had found out from their experiments and what they needed to do next.

From bedside to bench

In the 1930s, it was discovered that a female Xenopus laevis would ovulate if injected with the urine from a pregnant woman.

Xenopus laevis was to be the saviour of the egg-starved scientists, but it rose to prominence for another reason altogether. In the 1930s, it was discovered that a female X. laevis would ovulate if injected with the urine from a pregnant woman due to the presence of the hormone chorionic gonadotropin. For a while in the 1940s and 1950s, this was the only available pregnancy test, and many hospitals kept X. laevis for this purpose. However, not all hospitals were vigilant in keeping the frogs and many escaped! Unlike today, in these early years there were no clear guidelines for the care and treatment of animals in research.

From the 1950s onwards X. laevisgradually became the organism of choice for developmental studies. Important embryological techniques, such as grafting, which involves taking a piece of tissue and putting it somewhere else in the embryo, are very easy to do with high precision in X. laevis embryos because of their large size (usually 1mm to 1.3mm in diameter).

Using X. laevis embryos in the mid-1980s, it was shown that ‘inducing factors’ called fibroblast growth factors and activins are secreted by signalling centres in the frog. This signalling leads to certain patterns of development in the X. laevis embryo. Following this, other major classes of signalling molecules found in the cells of animals have subsequently been identified, allowing scientists to learn even more about how the frog and other vertebrates develop from embryo to adult.

A new frog on the block

X. laevis is allotetraploid (four copies of each chromosome, rather than two like us) which makes it very difficult to knock out a gene to investigate its function. It also has a long generation time, it takes a year for females to reach sexual maturity, making breeding experiments impractical. Therefore, X. laevis researchers looked to develop a simpler method to investigate the functions of genes and proteins in the development of the frog.

The genome of Xenopus tropicalis was sequenced in 2010 – the first sequence of an amphibian.

The solution came in the form of a close cousin of Xenopus laevis, Xenopus tropicalis. X. tropicalis is smaller than X. laevis, has a shorter life cycle (it matures in about four months) and has a small diploid genome (two copies of each chromosome rather than four). There were high hopes that X. tropicalis would have all the advantages of X. laevis and simpler genetics as well.

The genome of Xenopus tropicalis was sequenced in 2010. It was the first sequence of an amphibian. The high quality sequence has aided researcher’s using Xenopus tropicalis, to have a better understanding of its embryo development and cell biology.

Without the contributions of the African clawed frog our understanding of early development would not have progressed at such a rapid rate.

Studying both X. laevis and X. tropicalis has enabled scientists to discover much about the early three-dimensional development of the embryo after initial fertilisation. It has been particularly useful for the analysis of events occurring very early in development, such as the formation of the neural plate, which gives rise to the entire nervous system. However, there is still much work to be done to help us understand how organs develop, how tadpoles become frogs and how limbs and tails regenerate.

There are still considerable questions that are waiting to be answered, however, it is certain that without the contributions from research of the African clawed frog our understanding of early development would not have progressed at such a rapid rate.