Preface
The story of Xenopus as an experimental model system
seems like a version of the Grimm Brothers’ “The Frog
Prince.” Here, a frog, Xenopus laevis, also came from
humble beginnings, and with a little “tender loving care,”
it became a prince, or, as many would prefer, a “princess,”
for many felds of biomedical research and basic biology.
Once upon a time, the founders of experimental embryology used many different species of amphibians, including
a variety of newts and frogs. For half a century, pioneers,
including Wilhelm Roux, Hans Spemann, Thomas Hunt
Morgan, Oscar Hertwig, and others, used these species to
decipher many of nature’s secrets, including basic principles
in cell biology, neurobiology, morphogenetic movements,
cell communication, and the contributions of the genome.
Some of these breakthroughs were afforded the highest
accolades, such as the awarding of the 1935 Nobel prize to
Hans Spemann for the discovery of embryonic induction. In
parallel, some of these experimental models provided scientifc tools to study the effects of the environment on biological processes in early toxicological and teratogenic studies.
However, the inability to maintain or breed these animals in
the laboratory environment limited many of these studies.
In the 1930s, a new frog animal model caught the interest
of the medical and scientifc community. Initially introduced
to the clinic for performing pregnancy tests, Xenopus laevis,
also known as the African clawed frog, proved very resilient
in the laboratory environment. One of the consequences of
using Xenopus in pregnancy tests was its wide distribution
around the world, and colonies were established at multiple
universities and hospitals. The maintenance of these colonies revealed that Xenopus husbandry is very simple, and
eggs and embryos can be readily obtained year-round with
minimal effort. This frog species thrived in the laboratory,
effciently breeding to produce large numbers of eggs after
injection of readily available reproductive hormones. Since
then, many of the classical experiments previously performed in other amphibian models have been repeated and
expanded using Xenopus.
Each experimental model system has advantages and disadvantages, and the chapters in this book describe some of
the particular strengths of Xenopus as a vertebrate experimental model system to study basic biological principles and
human disease. Because amphibians are tetrapods, Xenopus
is closer evolutionarily to mammals, and in particular
humans, than fsh. More importantly, most of the biological and biomedical principles identifed and characterized
in Xenopus are generally applicable to all vertebrates. The
Xenopus laevis oocyte is relatively large in size (~1.4 mm
in diameter), and a female can lay from several hundred
to several thousand eggs in a single day. This large clutch
size provides an excellent source of biochemical materials
and has been used to study the cell cycle, DNA replication,
and chromatin structure. Beyond the clear advantages for
biochemical studies, the large clutch size allows performing rather complex experiments composed of multiple samples from a similar genetic background and large enough
sample sizes for statistical signifcance of the results. The
large size of the Xenopus oocyte also allows the easy use
of glass needles to inject the oocytes with mRNAs that can
undergo translation and subsequent post-translational processing into proteins that can be properly folded, chemically
modifed, and either retained intracellularly, integrated into
membranes, or secreted. Oocytes can also be injected with
chemicals, antibodies, DNA molecules, and other reagents
to study many biological processes.
An important direction in which Xenopus laevis became
a cornerstone was in the analysis of embryonic development.
The ease with which hundreds of embryos can be obtained
in a single clutch, allowing large samples, combined with
the external development that allows analysis of all developmental stages, were essential for characterizing basic principles of embryogenesis in vertebrates. Already from the early
studies, it was clear that amphibian embryos were amenable to microsurgical manipulation and transplantations;
Xenopus embryos proved no different and even particularly
resilient to this type of experiment. The egg’s large size
and its rapid development into an embryo became an asset
for the production and analysis of gene products following mRNA injection. The detailed fate maps of individual
cells made it possible to target microinjections to particular
regions, sometimes on one side of the embryo, thus minimizing off-target effects and providing an internal control
in each embryo. Thus, many basic principles of vertebrate
embryogenesis were elucidated using Xenopus embryos,
and numerous aspects in the characterization of signaling
pathways were worked out using Xenopus embryos. Over the
years, studies based on Xenopus have received worldwide
recognition and prizes, including the Nobel prize in 2012 to
Sir John Gurdon for the discovery of genetic reprogramming
of mature cells to pluripotency.
The allotetraploid genetic composition of Xenopus laevis
and its relatively long generation time (1–1.5 years) had initially posed a challenge for loss-of-function studies based on
mutants. These apparent “deal breakers” as a model system
drove research in directions that proved extremely fruitful
for our understanding of vertebrate embryogenesis. First,
the Xenopus community focused on the identif cation and
cloning of numerous novel genes central to almost every
developmental and regeneration process. In many instances,
this massive cloning effort helped identify and elucidate
signaling pathways, developmental processes, cellular morphogenesis, biochemical interactions, and many more processes. This focused cloning effort eventually resulted in a
massive collection of cDNA and EST clones that drove forward research in Xenopus and in multiple instances paved
the way for studies in other experimental model systems.
vii
The story of Xenopus as an experimental model system
seems like a version of the Grimm Brothers’ “The Frog
Prince.” Here, a frog, Xenopus laevis, also came from
humble beginnings, and with a little “tender loving care,”
it became a prince, or, as many would prefer, a “princess,”
for many felds of biomedical research and basic biology.
Once upon a time, the founders of experimental embryology used many different species of amphibians, including
a variety of newts and frogs. For half a century, pioneers,
including Wilhelm Roux, Hans Spemann, Thomas Hunt
Morgan, Oscar Hertwig, and others, used these species to
decipher many of nature’s secrets, including basic principles
in cell biology, neurobiology, morphogenetic movements,
cell communication, and the contributions of the genome.
Some of these breakthroughs were afforded the highest
accolades, such as the awarding of the 1935 Nobel prize to
Hans Spemann for the discovery of embryonic induction. In
parallel, some of these experimental models provided scientifc tools to study the effects of the environment on biological processes in early toxicological and teratogenic studies.
However, the inability to maintain or breed these animals in
the laboratory environment limited many of these studies.
In the 1930s, a new frog animal model caught the interest
of the medical and scientifc community. Initially introduced
to the clinic for performing pregnancy tests, Xenopus laevis,
also known as the African clawed frog, proved very resilient
in the laboratory environment. One of the consequences of
using Xenopus in pregnancy tests was its wide distribution
around the world, and colonies were established at multiple
universities and hospitals. The maintenance of these colonies revealed that Xenopus husbandry is very simple, and
eggs and embryos can be readily obtained year-round with
minimal effort. This frog species thrived in the laboratory,
effciently breeding to produce large numbers of eggs after
injection of readily available reproductive hormones. Since
then, many of the classical experiments previously performed in other amphibian models have been repeated and
expanded using Xenopus.
Each experimental model system has advantages and disadvantages, and the chapters in this book describe some of
the particular strengths of Xenopus as a vertebrate experimental model system to study basic biological principles and
human disease. Because amphibians are tetrapods, Xenopus
is closer evolutionarily to mammals, and in particular
humans, than fsh. More importantly, most of the biological and biomedical principles identifed and characterized
in Xenopus are generally applicable to all vertebrates. The
Xenopus laevis oocyte is relatively large in size (~1.4 mm
in diameter), and a female can lay from several hundred
to several thousand eggs in a single day. This large clutch
size provides an excellent source of biochemical materials
and has been used to study the cell cycle, DNA replication,
and chromatin structure. Beyond the clear advantages for
biochemical studies, the large clutch size allows performing rather complex experiments composed of multiple samples from a similar genetic background and large enough
sample sizes for statistical signifcance of the results. The
large size of the Xenopus oocyte also allows the easy use
of glass needles to inject the oocytes with mRNAs that can
undergo translation and subsequent post-translational processing into proteins that can be properly folded, chemically
modifed, and either retained intracellularly, integrated into
membranes, or secreted. Oocytes can also be injected with
chemicals, antibodies, DNA molecules, and other reagents
to study many biological processes.
An important direction in which Xenopus laevis became
a cornerstone was in the analysis of embryonic development.
The ease with which hundreds of embryos can be obtained
in a single clutch, allowing large samples, combined with
the external development that allows analysis of all developmental stages, were essential for characterizing basic principles of embryogenesis in vertebrates. Already from the early
studies, it was clear that amphibian embryos were amenable to microsurgical manipulation and transplantations;
Xenopus embryos proved no different and even particularly
resilient to this type of experiment. The egg’s large size
and its rapid development into an embryo became an asset
for the production and analysis of gene products following mRNA injection. The detailed fate maps of individual
cells made it possible to target microinjections to particular
regions, sometimes on one side of the embryo, thus minimizing off-target effects and providing an internal control
in each embryo. Thus, many basic principles of vertebrate
embryogenesis were elucidated using Xenopus embryos,
and numerous aspects in the characterization of signaling
pathways were worked out using Xenopus embryos. Over the
years, studies based on Xenopus have received worldwide
recognition and prizes, including the Nobel prize in 2012 to
Sir John Gurdon for the discovery of genetic reprogramming
of mature cells to pluripotency.
The allotetraploid genetic composition of Xenopus laevis
and its relatively long generation time (1–1.5 years) had initially posed a challenge for loss-of-function studies based on
mutants. These apparent “deal breakers” as a model system
drove research in directions that proved extremely fruitful
for our understanding of vertebrate embryogenesis. First,
the Xenopus community focused on the identif cation and
cloning of numerous novel genes central to almost every
developmental and regeneration process. In many instances,
this massive cloning effort helped identify and elucidate
signaling pathways, developmental processes, cellular morphogenesis, biochemical interactions, and many more processes. This focused cloning effort eventually resulted in a
massive collection of cDNA and EST clones that drove forward research in Xenopus and in multiple instances paved
the way for studies in other experimental model systems.
vii