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Medaka — a model organism from the far east

Key Points

  • Comparative studies of distantly related vertebrate species are essential to identify the conserved, as well as the species-specific, genetic and molecular mechanisms that underlie development and evolution. Medaka and zebrafish are ideal for this purpose, as both separated from their last common ancestor 110 million years ago.

  • The striking difference between the phenotypes that were recovered from developmental screens in medaka and in zebrafish indicates a non-overlapping spectrum of embryonic-lethal phenotypes.

  • The genetic resources established in medaka, such as inbred strains and genetic maps, allow mapping as well as positional cloning of spontaneous and induced mutations.

  • New technologies, such as transgenesis, enhancer trapping and availability of stem cells widen the experimental spectrum in medaka.

  • Like mammals, medaka has an XX, XY sex-determination system, but unlike higher vertebrates, full sex reversals can be obtained. Because sex determination in medaka seems to be at a very early stage of evolution, it might provide useful information on the evolution of sex-determination systems.

  • Mutants that specifically affect eye development, as well as gain-of-function experiments, in medaka have contributed to the general understanding of vertebrate eye development, complementing other vertebrate model systems.

  • Vertebrate genome evolution can be studied by comparative genomic approaches in medaka, fugu and zebrafish.

Abstract

Genome sequencing has yielded a plethora of new genes the function of which can be unravelled through comparative genomic approaches. Increasingly, developmental biologists are turning to fish as model genetic systems because they are amenable to studies of gene function. Zebrafish has already secured its place as a model vertebrate and now its Far Eastern cousin — medaka — is emerging as an important model fish, because of recent additions to the genetic toolkit available for this organism. Already, the popularity of medaka among developmental biologists has led to important insights into vertebrate development.

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Figure 1: Views on medaka.
Figure 2: Evolutionary relationships between fish models.
Figure 3: Mutant phenotypes that are unique to medaka.
Figure 4: Medaka fish that are transgenic for green fluorescent protein.
Figure 5: Producing sex-reversed medaka.
Figure 6: Schematic representation of vertebrate eye development.

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Acknowledgements

We are indebted to our colleagues F. Loosli, D. Arendt, A. Shimada, H. Mitani, C. Winkler, J.-N. Volff and all other members of the labs of the three authors for their input into the manuscript. We also appreciate the input of H. Kondoh, M. Furutani-Seiki and Y. Wakamatsu. We thank our colleagues in the field who shared their data with us before publication and apologize to all whose work could not be cited due to space limitations.

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Correspondence to Joachim Wittbrodt.

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DATABASES

LocusLink

Nodal

Pax6

Shh

Six3

SRY

Wnt

FURTHER INFORMATION

EST database: and Medaka Genome Initiative

Medakafish homepage

RZPD

Glossary

ZOOGEOGRAPHY

The discipline of biology that deals with the geographical distribution of animals.

MULTI-LOCUS TESTER STRAIN

Strain that is homozygous at several recessive loci and is used to detect induced recessive mutations in the germ line; the higher the number of marker loci, the higher the detection efficiency.

ENDOCRINE DISRUPTOR

An exogenous substance that changes endocrine function and causes adverse effects at the level of the organism, its progeny and/or the population.

INBRED STRAIN

A strain is considered inbred when it is homozygous at 99% of loci. This level of homozygosity can be achieved after at least 20 generations of successive brother–sister matings.

AFLP

A mapping method in which genomic DNA from different strains is PCR amplified using arbitrary primers. DNA fragments that are amplified in one strain, but not the other, are cloned, sequenced and used as polymorphic markers.

MORPHOLINO

Chemically modified oligonucleotide that behaves as an RNA analogue and has been used to interfere with gene function in fish. Because it interferes with translation, a morpholino is designed to complement the region around the translational start site of the target gene.

GERMINAL VESICLE STAGE

A stage during oocyte maturation in which the oocyte nucleus is located close to the surface of the egg cell and is clearly visible.

MIDBLASTULA TRANSITION

A stage during embryogenesis when zygotic transcription starts and cell divisions become asynchronous.

PSEUDOTYPED RETROVIRUS

Retrovirus, the host range of which has been altered; they were initially developed for human gene therapy.

TRANSGENESIS FREQUENCY

The frequency of injected embryos that are stably transgenic and transmit the transgene to the next generation.

GERM-LINE TRANSMISSION RATE

The rate of transgenic F1 offspring that arise from a cross between a transgenic founder fish and a wild-type fish. It reflects germ-line mosaicism, depends on the time point of integration and cannot exceed 50%.

ENHANCER TRAPPING

A strategy that uses targeting vectors to trap or isolate enhancers of nearby genes. The inserted vector sequence acts as a tag that facilitates cloning of the neighbouring gene.

FACS SORTING

A method whereby dissociated and individual living cells are sorted, in a liquid stream, according to the intensity of fluorescence that they emit as they pass through a laser beam.

MIDBLASTULA

Early stage of fish embryonic development corresponding to 1,000 totipotent cells that form a cap on the yolk.

EUPLOID KARYOTYPE

Complete chromosome set, without any deletions or additions of whole chromosomes or chromosome fragments.

EMBRYOID BODY

Ball-like structure that forms from embryonic stem cells when they are kept in suspension culture.

DEGREE OF CHIMERISM

The proportion of differentiated embryonic cells that are derived from the embryonic stem cells.

CYPRINID FISH

A large group of freshwater fish species that includes the common carp, goldfish and zebrafish.

CLASS

A taxonomic group.

GONOCHORISM

The presence of separate male and female sexes in a species (opposite to hermaphrodism).

GASTRULATION

A morphogenetic process in embryogenesis during which the mesoderm is formed.

EYE FIELD

An epithelial eye precursor in the anterior neuroectoderm.

NEURAL PLATE

Ectodermally derived precursor of the brain and spinal cord that forms at the beginning of neurulation.

ANLAGE

A precursor tissue before its determination and differentiation.

MIDLINE

The notochord and its anterior extension, the prechordal plate, which are located in the ventral midline of the developing embryo.

NEURULA

A developmental embryonic stage at the end of gastrulation that corresponds to the formation of the neural plate.

PARALOGUE

Homologous gene that originates by gene duplication.

ORTHOLOGUE

Homologous gene in different species the lineage of which derives from a common ancestral gene without gene duplication or horizontal transmission.

RADIATION HYBRID PANEL

A set of DNA samples prepared from a collection of radiation hybrids, each of which is a clonal population of cells that are derived by the fusion of lethally X-irradiated donor cells with mammalian cells. Such cell lines can be used to create a physical map of the donor genome.

CILIARY MARGIN

An area at the margin of neuroretina and pigmented epithelium that contains cells with stem-cell characteristics.

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Wittbrodt, J., Shima, A. & Schartl, M. Medaka — a model organism from the far east. Nat Rev Genet 3, 53–64 (2002). https://doi.org/10.1038/nrg704

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