Hematopoiesis

Our laboratory is interested in the development of the blood-forming, or hematopoietic, system in the vertebrate embryo. Most of our studies are aimed at understanding how the hematolymphoid system arises in the zebrafish embryo from the first hematopoietic stem cells. We are leveraging the many advantages that the zebrafish system offers to study the ontogeny of hematopoiesis. These include the easy visualization of blood cells in the translucent embryo and the ability to dissect genetically the pathways important for blood cell specification, maintenance and function.

Movie 1. Tail of an adult animal carrying b-Actin:eGFP and GATA-1:dsRED transgenes. In hematopoietic tissues in these animals, all leukocytes are green and all erythrocytes are red. These double transgenic animals are routinely used as donors in transplantation settings to track multilineage hematopoiesis in wild-type or mutant recipients.

Immunity

We have recently initiated studies to develop an understanding of the ontogeny of immunity in the zebrafish embryo. Fertilization occurs externally in zebrafish, and the resulting embryos are autonomous from the beginning. Early embryos placed into solutions containing high bacterial titres are extremely resistant to infection. We are examining the components of this early immunity, with the goals of identifying the effectors of innate immunity, developing models of bacterial infection, and determining when and where antigen presentation occurs to prime the adaptive immune response. Our ultimate goal is to observe the immune response in real time in living animals through the use of multiparameter fluorescent imaging. We can then begin to perform genetic analyses to understand the molecular bases of observed immune cell behavior.

Movie 2. Caudal region of a wild-type embryo injected with Stapholococcus aureus labeled with FITC. Immediately after injection, bacteria circulate rapidly throughout the embryo.

Movie 3. Within two hours, the vast majority of bacteria have been cleared by large, motile phagocytes. In this timelapse movie, the macrophages can be seen as FITC+ cells migrating throughout the tail of the embryo.