Video of a live zebrafish with melanoma (Zon lab).
Zebrafish that express a mutated form of the human BRAF oncogene develop black-pigmented moles. When they were also made to be deficient for the p53 gene, the moles developed into invasive melanomas resembling human cancers.
Video of the Casper fish heart beating (Zon lab)
"Casper" is a new zebrafish model that will facilitate metastasis studies. It remains transparent as an adult allowing direct visualization of metastatic cancer cells as they spread.
A narrated 3D animation about the process of metastasis.
The class will go with Shibani to the Moens lab after the lecture from ~3-3.30pm. Based on topics discussed in the lecture, we will do the following:
1. Distinguish between zebrafish embryos/larvae at different developmental stages, and discuss the impact of temperature on the rate of development.
2. Observe the heartbeat in the embryo and discuss the practical aspects of gridlock mutant and chemical genetics screen covered in the lecture.
3. Identify various characteristics of the embryos under the microscope, such as the developing eye, ear, heart, circulating blood cells, cerebellum, yolk sac, pigmentation patterns, notochord and twitching motion in the late stages.
Overall we will develop an appreciation of why the large, transparent embryos that develop external to the female are excellent models for both developmental and cancer biologists.
Zebrafish (Danio rerio)
Lecture videos are available for viewing in the left column. They will be used to illustrate points about the following:
Required/Encouraged Reading
1. A great review covering history, pros/cons, techniques, general zebrafish disease models.
"Animal models of human disease: zebrafish swim into view" by Graham Lieschke and Peter Currie.
2. This review specifically and comprehensively deals with zebrafish models of cancer.
"Zebrafish as a Cancer model" by Harma Feitsma and Edwin Cuppen.
Additional Reading
1. Review covering the history of zebrafish research.
" Headwaters of the zebrafish -- emergence of a new model vertebrate." by David Grunwald and Judith Eisen.
2. Review about cancer biology in zebrafish covers chemical screens and TILLING.
"Cancer genetics and drug discovery in the zebrafish" by Howard Stern and Leonard Zon".
3. Generating the transparent "Casper" fish. See Figure 4 for melanoma metastasis study.
"Transparent Adult Zebrafish as a Tool for In Vivo Transplantation Analysis" by White RM et al.
4. Metastasis study using a novel zebrafish xenograft model.
"High-resolution imaging of the dynamic tumor cell–vascular interface in transparent zebrafish" by Stoletov K et al.
FHCRC
scientists working with fish model systems:
1. Cecilia Moens: Vertebrate brain regionalization during early development.
2. Mark Roth: Suspended animation and "metabolic hibernation".
3. Katie Peichel: Mechanisms underlying evolutionary processes in the threespine stickleback fish.
These are excellent resources for zebrafish information.
1. An online database for collects, curates, and disseminates information about zebrafish biology.
2. A comprehensive free online guide for laboratory use of zebrafish (Danio rerio).
3. A resource center that acquire resources from the research community, maintains them, and redistributes them upon request for a nominal price
Zebrafish International Resource Center
4. Educational resource for zebrafish courses. See the fun "Virtual Experiments" section for movies of the beating hearts in casanova mutants and the developmental staging experiment.