zebra fish facility
Advantages of Using Zebrafish as a Model Biological System
Aquatic models have a long history in toxicology and developmental biology. The zebrafish is an important vertebrate model organism in scientific research. Zebrafish are notable for their regenerative abilities and have been modified by scientists to produce several transgenic strains; the Zebrafish Information Network (ZFIN) provides up-to-date information about currently known wild-type strains. Recently it has been widely explored in the study of different models of pathological and normal biological phenomena including cancers, angiogenesis, inflammation response, cell regeneration and functional neuron circuits.
Advantages of Zebrafish over rodent model systems:
- Rapid external development
Unlike murine embryos, zebrafish embryos are fertilized and developed externally and also rapidly. This facilitates a number of technical manipulations, including microinjection, cell transplantation, microsurgery and cell ablation. Precursors to all major organs appear within 36 hours of fertilization, and hatching takes place 12 to 36 hours later, depending on the embryo's internal conditions and the external temperature. Swimming and feeding behavior begin about 36 hours later. These benefits allow straightforward phenotypic analysis of early embryonic defects and compound effects, which are often difficult to observe in the murine models.
- Transparent embryos
Because the zebrafish embryo is transparent, it is possible to easily and directly visualize cells during development. By using transgenic lines in which fluorescent proteins are driven by a tissue-specific promoter, it is possible to label different cell types allowing direct visualization of tissue morphogenesis as it occurs in the developing embryo. Transparency also facilities high throughput forward genetics screening using automated microscopy.
- Amenable to genetic and cellular manipulation
Because zebrafish embryos develop externally, it is possible to perform a variety of technical manipulations, including microinjections at early stages to introduce DNA, RNA or proteins. By combining this approach with transgenic and mutant lines, the behavior of mutant cells in a wild-type tissue can be observed.
- Medical research applications
Zebrafish has been actively studied in many areas of medical research. For example, zebrafish have been used to make several transgenic models of cancer, including melanoma, leukemia, pancreatic cancer and hepatocellular carcinoma. In cardiovascular research, the zebrafish has been used to model blood clotting, blood vessel development, heart failure, congenital heart defects and kidney disease. In research into acute inflammation, researchers have established a zebrafish model of inflammation that allows detailed study of the genetic controls of inflammation and the possibility of identifying potential new drugs. Other reported medical research applications include infectious diseases, retinal damage repair and drug discovery.
The ZFIQ (Zebrafish image quantitator) software toolkit was developed by the research group led by Stephen Wong, PhD, PE, at Houston Methodist — a large part of the development effort done while his group was part of the Harvard Center for Neurodegeneration and Repair (HCNR) at Harvard Medical School. ZFIQ is a result of collaboration with many neuroscientists over the years, including Weiming Xia, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Jarema Malicki, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School; and Scott Holley, Department of Molecular, Cellular and Developmental Biology, Yale University.
The ZFIQ software provides a set of practical and effective image analysis tools for quantitative, reproducible and accurate interpretation of zebrafish imaging data, in particular, for streamlined processing and analysis of bioimaging data. The design of ZFIQ is modular such that new applications and modules can be added into the toolkit. The ZFIQ software, which is available free, can also be used as a platform for integrating and exchanging data, algorithms and ideas among zebrafish scientists, developmental biologists and biomedical researchers. In addition, for specialized image data analysis needs, users can request the service of the Biomedical Informatics Support Core at Houston Methodist.
Current Fish Lines
- AB: a wild type of zebrafish
- Tg(mnx1:GFP)ml2/+ (AB): all the neurons are labeled with GFP-expression protein
- Transgenic GCaMP-HS with Gal4FF-UAS: double transgenic line to monitor the activities of a specific neuronal circuit
Stephen Wong, Ph.D, PE
Kemi Cui, M.D., Ph.D
Tieling Zhou, B.S, Research Assistant I