Use of zebrafish chemical genetics to find inducers of stem cells

TOXI 5

Leonard I. Zon, zon@enders.tch.harvard.edu, Karp Family Research Laboratories, Rm 7211, HHMI/Children's Hospital, 300 Longwood Ave., Boston, MA 02115
The zebrafish is a powerful system for studying developmental biology and disease. Over the past several years, the zebrafish has been pioneered as a model for chemical genetics. Each female zebrafish has 300 babies per week and their small size allows more high throughput screening using embryos. We have utilized zebrafish embryos to examine the number of hematopoietic stem cells (HSC) and have done a screen for chemicals that induce HSC number. After screening a library of known chemicals, chemicals were found that increase hematopoietic stem cells. These chemicals involved the prostaglandin synthesis pathway. We subsequently used adult zebrafish and adult mice to prove that the prostaglandins affect stem cell homeostasis. Our screens using the zebrafish in cancer models have similarly found chemicals that suppress cancer pathways. In summary, the zebrafish is an excellent model for chemical genetics to find bioactive compounds.