The post-Human Genome Project challenge is to define the function of genes, and large-scale high-throughput mouse mutagenesis is one of the best avenues for determining mammalian gene function. Genetic manipulations in the mouse are extremely powerful. Inbred strains of mice provide defined backgrounds to study complex genetic interactions. Transgenesis to produce mutations that over express or eliminate the function of genes has established the mouse as a model organism for studying mammalian gene functions. Recently, forward genetics using chemical mutagenesis has made the mouse a powerful organism to define gene functions and model human diseases. Our lab exploits each of these genetic techniques in a variety of projects designed to dissect the molecular genetic basis for hematopoiesis. Hematopoiesis is a complex process that involves progressive differentiation steps towards lineage commitment from a self-renewing stem cell. In mammals, differentiation of hematopoietic cells takes place in multiple sites and times during development: the fetal yolk sac and mesodermal aortic/gonadal region, the fetal liver, and the bone marrow. Projects in the lab focus on different stages of hematopoiesis and vasculogenesis, but all utilize the unique power of mouse genetics.