Introduction to Xenopus, the frog model
Xenopus are an invaluable tool to study vertebrate embryology and development, basic cell and molecular biology, genomics, neurobiology and toxicology and to model human diseases.
Studying model organisms, such as Xenopus, allows us to decipher how regulatory and interactions networks direct embryonic development, how they adapt during aging and under environmental stress, and how they become dysregulated to cause disease, malformations and birth defects.
Several features make <Xenopus eggs and embryos an outstanding tool in biomedical research.
- embryos tolerate extensive manipulation (e.g. single cell , germ layer dissections, tissue transplantations)
- easy to inject of a range of materials (e.g. nucleic acids, proteins, whole nuclei) into whole embryo or specific cells
- cell fate of each early embryonic cell is known, allowing targeted gene knock-out, knockdown and overexpression studies
- eggs and embryos provide abundant source for high-throughput biochemical studies
- cell-free extracts made from Xenopus oocytes are a premier in vitro system for studies of fundamental aspects of cell and molecular biology
- Xenopus oocytes are a leading system for studies of ion transport and channel physiology
- Xenopus oocytes widely used assay environmental toxicology
- large-scale genetic screens has identified genes involved in diverse developmental and physiological processes
Background of Xenopus
Xenopus is a genus of African frogs that are commonly known as the African clawed frogs. Two species of Xenopus are regularly used by biologists, Xenopus laevis and Xenopus tropicalis. Both species are fully aquatic, and are easy to maintain in captivity. Frog eggs are large (~1.2mm diameter), produced in large quantities, and easy to manipulate. This makes them a valuable tool to investigate the early period of embryonic development. Egg production can be stimulated by injection of chorionic gonadotropin. In the 1930's, doctors used Xenopus as a simple pregnancy test for women- because this hormone is present in the urine of a pregnant woman, the frog would be induced to lay eggs. Biologists utilize this same method to induce the production of eggs on demand in the laboratory. The frogs are then rested for a few months, when they can be induced again. Very few species of frog can be induced to produce eggs in such a controlled manner, and this is another reason why Xenopus is so popular with developmental and cell biologists.
Frog embryos develop externally, allowing experiments to be performed prior to, or directly following fertilization. Rapid embryo growth and development means that within a couple of days, a tadpole has a fully functional set of organs, and it can be examined to determine if any experimental intervention has had an effect.
Comparing the two species, X.tropicalis has a much shorter life cycle than does X. laevis, growing to adult in 4 months compared with 12 months, making it a faster system to study. X. tropicalis is also diploid (i.e., it has two sets of chromosomes), while X. laevis is allotetraploid (a form of tetraploid, i.e. it has four sets of chromosomes), thus X.tropicalis is a more simple model for genetic studies.
The genomes of both X. laevis and X. tropicalis have been sequenced. They display remarkable structural similarity with the human genome (Hellsten et al. ,2010) meaning that findings from Xenopus provide insights into many human conditions and diseases.
Advantages of Xenopus as a Model Organism
Category: | C. elegans | Drosophila | Zebrafish | Xenopus | Chicken | Mouse |
---|---|---|---|---|---|---|
Broodsize | 250-300 | 80-100 | 100-200 | 500-3000+ | 1 | 5-8 |
Cost per embryo | low | low | low | low | medium | high |
High-throughput multiwell-format screening | good | good | good | good | poor | poor |
Access to embryos | good | good | good | good | poor | poor |
Micro-manipulation of embryos | limited | limited | fair | good | good | poor |
Genome | known | known | known | known | known | known |
Genetics | good | good | good | fair | none | good |
Knockdowns (RNAi, morpholinos) | good | good | good | good | limited | limited |
Transgenesis | good | good | good | good | poor | good |
Evolutionary distance to human | very distant | very distant | distant | intermediate | intermediate | close |
Adapted from Wheeler & Brändli 2009 Dev Dyn 238:1287-1308.
Experimental organisms such as frogs (X. laevis and X. tropicalis), nematode worms (C. elegans), fruit flies (Drosphilia spp.), zebrafish (Danio rerio) , chicken (Gallus Gallus) and mice (Mus musculus) are used to discover the molecular mechanisms fundamental to life, thereby providing a shortcut to understanding human biology. Each model organism has its advantages and disadvantages, and these are compared in the table to the right (adapted from Wheeler and Brändli 2009).
Phylogenetic tree showing the main animal models commonly used in biomedical research and their evolutionary relationships. The divergence time, in millions of years (Mya), is based on multiple gene divergence and protein divergence studies.
Adapted from Wheeler & Brändli 2009 Dev Dyn 238:1287-1308.
As a group, amphibians are phylogenetically well positioned for comparisons to other vertebrates, having diverged from the amniote lineage (mammals, birds, reptiles) some 360 million years ago. The comparison with mammalian and bird genomes also provides an opportunity to examine the dynamics of tetrapod chromosomal evolution. The genomes of both X. laevis and X. tropicalis species have been sequenced and display remarkable structural similarity with the human genome, meaning that findings from Xenopus provide insights into many human conditions and diseases.
So in summary, Xenopus is a valuable tool because they are:
- hardy, fully aquatic and easy to maintain in the laboratory
- produce eggs year-round
- eggs are a reliable and flexible material for research
- embryos are a good model for vertebrate development
- genetically similar to humans thus a good model for human disease
Read more about
Biological Discoveries and Biomedical Research using Xenopus (coming soon).