viii
Preface
Second, the apparent lack of genetic tools for a couple of
decades drove the analysis of gene function in Xenopus laevis to rely on gene-specifc antisense oligonucleotides, overexpressed dominant-negative protein variants, antimorphic
protein constructs, and pharmacological manipulation of
protein function.
The complex genome composition of Xenopus laevis necessitated the search for strategies to enable genetic approaches.
One of the solutions to this genetic quest culminated in the
introduction of Xenopus tropicalis, a true diploid Xenopus
species with a short generation time (4–6 months) similar to
mouse and zebraf sh. X. tropicalis research benef ted from
the wealth of methods already developed for X. laevis, which
were rapidly adapted for the newcomer. Also, due to the high
similarity in the genome sequence, gene discovery in X. tropicalis surged forward based on the clones available from X.
laevis. The story of these two truly complementary models
is a story of real cross-pollination. As a true diploid, the X.
tropicalis genome project was completed in parallel to mammals. The diffculties of sequencing the allotetraploid X. laevis genome could fnally be solved using the high sequence
homology to X. tropicalis as a reference genome. In parallel,
methods were developed in both Xenopus species to generate transgenic strains as well as TALEN and CRISPR/Cas9
genome editing. Even with the longer generation time, genetically modif ed X. laevis lines are becoming mainstream in
analyzing normal developmental processes and generating
disease models.
Close to a century and a half of amphibian-based research
led to an extensive convergence to Xenopus as the main
model system. This is not to say that it is exclusive, as other
Xenopus species are incorporated for evolutionary studies,
other frog species are used for neurophysiological research,
and axolotl plays a major role in regeneration studies. With
the extensive genome information for laevis and tropicalis
and the genome editing technologies eff ciently implemented
to generate mutations, both species have surged forward
as excellent model systems in biomedical research. More
importantly, Xenopus is an excellent model system to recapitulate many aspects of human disease and the in-depth study
of its etiology. The ease of pharmacological manipulation in
Xenopus has also allowed the study of chemically induced
birth defects and disease. The large clutch size together with
the effcient implementation of genome editing technologies
allow the performance of relatively rapid disease studies and
screens. These studies initially analyze founder animals,
overcoming the need to establish genetically modif ed lines
and allowing faster analysis of disease-causing changes.
One aspect that signifcantly contributed to advancing
Xenopus as a major model system was a collaborative and
interactive community. In 1984, two leaders in the f eld of
developmental biology who utilized Xenopus, Igor Dawid
(NIH) and John Gurdon (Cambridge University), brought
together a group of about 20 international investigators to
discuss their research interests and deliberate on the advantages of having a regular meeting focused on Xenopus developmental genetics. Thus was born the International Xenopus
Conference, which has been held every two years since then.
Over the years, the conference has expanded to encompass
cell biology, neurobiology, regeneration, and disease models.
In addition, NIH-supported workshops in the 1990s led to
the development of critical research resources for the community, and similar community-organized meetings have
continued on a biannual basis as the Xenopus Resources and
Emerging Technologies meeting. These truly international
efforts of several hundred laboratories have signif cantly
contributed to the many advances that are summarized in
the chapters presented in this book.
Thus, this humble frog was transformed into a prince,
or princess, by the dedication and persistence of many
researchers, and by an interactive and supportive community. The chapters of this book summarize some of the
advantages of working with Xenopus in biomedical research
and some of the major contributions of Xenopus to our
biological knowledge. This collection shows how and why
Xenopus-based research is not only poised but has already
made major contributions to our understanding of human
biology and disease.
Abraham Fainsod and Sally A. Moody
Preface
Second, the apparent lack of genetic tools for a couple of
decades drove the analysis of gene function in Xenopus laevis to rely on gene-specifc antisense oligonucleotides, overexpressed dominant-negative protein variants, antimorphic
protein constructs, and pharmacological manipulation of
protein function.
The complex genome composition of Xenopus laevis necessitated the search for strategies to enable genetic approaches.
One of the solutions to this genetic quest culminated in the
introduction of Xenopus tropicalis, a true diploid Xenopus
species with a short generation time (4–6 months) similar to
mouse and zebraf sh. X. tropicalis research benef ted from
the wealth of methods already developed for X. laevis, which
were rapidly adapted for the newcomer. Also, due to the high
similarity in the genome sequence, gene discovery in X. tropicalis surged forward based on the clones available from X.
laevis. The story of these two truly complementary models
is a story of real cross-pollination. As a true diploid, the X.
tropicalis genome project was completed in parallel to mammals. The diffculties of sequencing the allotetraploid X. laevis genome could fnally be solved using the high sequence
homology to X. tropicalis as a reference genome. In parallel,
methods were developed in both Xenopus species to generate transgenic strains as well as TALEN and CRISPR/Cas9
genome editing. Even with the longer generation time, genetically modif ed X. laevis lines are becoming mainstream in
analyzing normal developmental processes and generating
disease models.
Close to a century and a half of amphibian-based research
led to an extensive convergence to Xenopus as the main
model system. This is not to say that it is exclusive, as other
Xenopus species are incorporated for evolutionary studies,
other frog species are used for neurophysiological research,
and axolotl plays a major role in regeneration studies. With
the extensive genome information for laevis and tropicalis
and the genome editing technologies eff ciently implemented
to generate mutations, both species have surged forward
as excellent model systems in biomedical research. More
importantly, Xenopus is an excellent model system to recapitulate many aspects of human disease and the in-depth study
of its etiology. The ease of pharmacological manipulation in
Xenopus has also allowed the study of chemically induced
birth defects and disease. The large clutch size together with
the effcient implementation of genome editing technologies
allow the performance of relatively rapid disease studies and
screens. These studies initially analyze founder animals,
overcoming the need to establish genetically modif ed lines
and allowing faster analysis of disease-causing changes.
One aspect that signifcantly contributed to advancing
Xenopus as a major model system was a collaborative and
interactive community. In 1984, two leaders in the f eld of
developmental biology who utilized Xenopus, Igor Dawid
(NIH) and John Gurdon (Cambridge University), brought
together a group of about 20 international investigators to
discuss their research interests and deliberate on the advantages of having a regular meeting focused on Xenopus developmental genetics. Thus was born the International Xenopus
Conference, which has been held every two years since then.
Over the years, the conference has expanded to encompass
cell biology, neurobiology, regeneration, and disease models.
In addition, NIH-supported workshops in the 1990s led to
the development of critical research resources for the community, and similar community-organized meetings have
continued on a biannual basis as the Xenopus Resources and
Emerging Technologies meeting. These truly international
efforts of several hundred laboratories have signif cantly
contributed to the many advances that are summarized in
the chapters presented in this book.
Thus, this humble frog was transformed into a prince,
or princess, by the dedication and persistence of many
researchers, and by an interactive and supportive community. The chapters of this book summarize some of the
advantages of working with Xenopus in biomedical research
and some of the major contributions of Xenopus to our
biological knowledge. This collection shows how and why
Xenopus-based research is not only poised but has already
made major contributions to our understanding of human
biology and disease.
Abraham Fainsod and Sally A. Moody