The National Institute of Diabetes and Digestive and Kidney Diseases, along with 19 other NIH institutes, sponsors initiatives to develop resources for zebrafish research.
This trans-NIH effort is overseen by the Trans-NIH Zebrafish Coordinating Committee, under the co-chairmanship of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Child Health and Human Development (NICHD). Other participating institutes are the National Cancer Institute; the National Eye Institute; the National Heart, Lung, and Blood Institute; the National Human Genome Research Institute; the National Institute of Alcohol Abuse and Alcoholism; the National Institute on Deafness and Other Communication Disorders; the National Institute on Drug Abuse; the National Institute of General Medical Sciences; the National Institute of Mental Health; the National Institute of Neurological Disorders and Stroke; the National Institute of Allergy and Infectious Diseases; the Center for Scientific Review; the National Insitute of Environmental Health Sciences; the National Institute on Aging; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Dental and Craniofacial Research; the National Library of Medicine; and the National Center for Research Resources.
The Zebrafish Model
Mutational analysis of development has proven to be a powerful tool to determine the events that result in patterning and morphogenesis of the embryo. Mutational studies combined with genetic combinatorial analyses can identify specific genes that dictate embryonic development and clarify the pathways in which they function. Experimentation in Drosophila melanogaster and Caenorhabditis elegans has established that remarkable evolutionary conservation exists of the genetic programs that determine not only embryo formation, including such early patterning events as formation of the embryonic axes, but also later events such as development of eye, heart, and other organs. Assessment of mutations affecting development in the mouse has provided a wealth of information about post-natal maturation. However, the mouse embryo is inaccessible throughout much of its development. In addition, the relatively long generation time and substantial costs of maintaining large mouse colonies have limited the applicability of genetic approaches.
The zebrafish, Danio rerio, has a number of valuable features as a model organism for the study of vertebrate development. Many features of zebrafish development have been characterized, including early embryonic patterning and some aspects of cell fate and lineage determination. The embryos are transparent and accessible throughout development. It is possible not only to generate not only haploid progeny, which are viable for up to five days, but also homozygous diploid progeny that carry only maternal (or paternal) genetic information. Because of their relatively short reproductive cycle, the large number of progeny that can be produced, and the relatively small space needed to maintain large numbers of offspring, the zebrafish is an efficient vertebrate model system for genetic analysis. Large-scale genetic screens have yielded much important information about vertebrate organogenesis and development.
Researchers have also begun to use the zebrafish model to study human disease. Mutations have been characterized that mimic many different human diseases, including dilated cardiomyopathies (pickwick), Usher syndromes 1B and 1D (mariner and sputnik), maturity onset diabetes of the young type V and glomerulocystic kidney disease (vHnf1), holoprosencephaly (sonic you), and porphyrias (yquem, dracula, sauternes). The use of genomics tools to transiently ablate expression of specific genes has also allowed researchers to investigate the molecular bases of various human genetic diseases.
The rapid pace of zebrafish research depends on the availability of appropriate tools and information. The Wellcome Trust is supporting the production of a complete zebrafish genomic sequence at the Sanger Institute. In the past, the NIH has supported large efforts to improve genetic maps, and generate a full-length cDNA collection of over 11,000 genes (zgc.nci.nih.gov). Current initiatives aim to enhance infrastructure to fully exploit the power of research with this organism, and to support additional genetic screens.
Project Officer (NIDDK): Rebekah S. Rasooly, Ph.D., 301-594-6007.
Program Announcement Requests:
Enhancing Zebrafish Research with Research Tools and Techniques
Genetic Screens to Enhance Zebrafish Research (NICHD)