157
produced in his lab are still alive in research facilities throughout the world and used to
provide answers to human and animal health issues.8
The How and Why of Using Zebrafish
The zebrafish is the first vertebrate proven amenable to large-scale genetic screening pre-
viously used so successfully in fruit flies and worms. It has many features that make it an
excellent model organism for studying development in vertebrates.
The embryos develop outside the mother and are transparent, so they can be easily
viewed and manipulated. The transparency of the embryos has become one of the leading
reasons for using them, as it allows researchers to watch the morphological changes that
occur during development.
Transparency also means that a naturally fluorescing protein called green fluorescent
protein can be used to label individual cells, organs and organelles.9 Mutations induced by
chemicals, radiation or viral insertion cause visible changes (phenotypes) that can be read-
ily observed in this vertebrate.10
The zebrafish has several advantages as a model for studying vertebrate developmen-
tal processes, including small size, easy care and rapid generation time. In addition, the
embryo develops from eggs that are externally fertilized. Because of their transparency,
the embryos can be continuously observed under light microscopy. Mutagenesis screens
can detect defects in early organ development and late organ function.
Because the fish is a vertebrate, its genetic program is more similar to that of mam-
mals than invertebrate models. The evolutionary divergence of fish from the mammalian
lineage occurred roughly 300 million years ago. This level of divergence is useful because
most organs among the vertebrates appear generally similar in form, and thus genes
involved in zebrafish organ formation have human analogs.11
Zebrafish can be used to discover psychoactive drugs. In the past, in vitro screening
assays could not be used to recreate the complex network interactions of whole organisms,
thus it was not possible to predict how small molecules would alter complex behaviors.
Recently discovered methods can now employ zebrafish developmental processes as a
high throughput screen for small molecules that are designed to alter larval zebrafish
locomotor behavior.12
Recently, researchers have discovered the zebrafish’s remarkable ability to mend a
damaged heart. Mature cardiocytes (cardiac muscle cells) near the injury site detach from
one another and lose their typical shape to make it possible to start dividing again to
replace lost tissue. Within two weeks, the new heart tissue can receive electrical signals
in the same manner as normal, healthy heart tissue. Figuring out exactly how zebrafish
accomplish their self repair could help scientists find ways to trigger similar regeneration
in human patients.13
Zebrafish mutants have been used to study the development of tumors that arise
from adenomatous polyps in the colon. Loss of the adenomatous polyposis coli (APC)
gene is a major trigger for colorectal cancer, the leading cause of cancer-related deaths in
the Western world. Studies have helped to understand the complex regulatory processes
involved and could result in better methods of early detection and treatment.14
Researchers have also been able to stimulate the development of a type of leukemia—
T cell acute lymphoblastic leukemia—in zebrafish. They fused the Myc gene, which
plays an important role in human leukemia, to a zebrafish gene that works exclusively in
lymphoid cells. Cancer developed in virtually all fish that carried a functional Myc gene.
Creating zebrafish that develop leukemia will enable scientists to screen thousands of
zebrafish genes for mutations that contribute to the disease and to test the effect of various
anti-cancer agents.15
Zebrafish: A Medical Research Bonanza
produced in his lab are still alive in research facilities throughout the world and used to
provide answers to human and animal health issues.8
The How and Why of Using Zebrafish
The zebrafish is the first vertebrate proven amenable to large-scale genetic screening pre-
viously used so successfully in fruit flies and worms. It has many features that make it an
excellent model organism for studying development in vertebrates.
The embryos develop outside the mother and are transparent, so they can be easily
viewed and manipulated. The transparency of the embryos has become one of the leading
reasons for using them, as it allows researchers to watch the morphological changes that
occur during development.
Transparency also means that a naturally fluorescing protein called green fluorescent
protein can be used to label individual cells, organs and organelles.9 Mutations induced by
chemicals, radiation or viral insertion cause visible changes (phenotypes) that can be read-
ily observed in this vertebrate.10
The zebrafish has several advantages as a model for studying vertebrate developmen-
tal processes, including small size, easy care and rapid generation time. In addition, the
embryo develops from eggs that are externally fertilized. Because of their transparency,
the embryos can be continuously observed under light microscopy. Mutagenesis screens
can detect defects in early organ development and late organ function.
Because the fish is a vertebrate, its genetic program is more similar to that of mam-
mals than invertebrate models. The evolutionary divergence of fish from the mammalian
lineage occurred roughly 300 million years ago. This level of divergence is useful because
most organs among the vertebrates appear generally similar in form, and thus genes
involved in zebrafish organ formation have human analogs.11
Zebrafish can be used to discover psychoactive drugs. In the past, in vitro screening
assays could not be used to recreate the complex network interactions of whole organisms,
thus it was not possible to predict how small molecules would alter complex behaviors.
Recently discovered methods can now employ zebrafish developmental processes as a
high throughput screen for small molecules that are designed to alter larval zebrafish
locomotor behavior.12
Recently, researchers have discovered the zebrafish’s remarkable ability to mend a
damaged heart. Mature cardiocytes (cardiac muscle cells) near the injury site detach from
one another and lose their typical shape to make it possible to start dividing again to
replace lost tissue. Within two weeks, the new heart tissue can receive electrical signals
in the same manner as normal, healthy heart tissue. Figuring out exactly how zebrafish
accomplish their self repair could help scientists find ways to trigger similar regeneration
in human patients.13
Zebrafish mutants have been used to study the development of tumors that arise
from adenomatous polyps in the colon. Loss of the adenomatous polyposis coli (APC)
gene is a major trigger for colorectal cancer, the leading cause of cancer-related deaths in
the Western world. Studies have helped to understand the complex regulatory processes
involved and could result in better methods of early detection and treatment.14
Researchers have also been able to stimulate the development of a type of leukemia—
T cell acute lymphoblastic leukemia—in zebrafish. They fused the Myc gene, which
plays an important role in human leukemia, to a zebrafish gene that works exclusively in
lymphoid cells. Cancer developed in virtually all fish that carried a functional Myc gene.
Creating zebrafish that develop leukemia will enable scientists to screen thousands of
zebrafish genes for mutations that contribute to the disease and to test the effect of various
anti-cancer agents.15
Zebrafish: A Medical Research Bonanza