Mast Cell Development and Function in the Zebrafish

Abstract

The many advantages of the zebrafi sh model provide a unique opportunity to integrate the tools of developmental embryology, transgenesis, and functional assays to elucidate the molecular pathways underlying hematopoiesis and for modeling human blood diseases. These methodologies have recently been applied to the zebrafi sh mast cell lineage and have resulted in a better understanding of vertebrate mast cell biology. By employing whole-mount in situ hybridization alone and in combination with co-localization approaches, fl uorescence-activated cell sorting (FACS), and morpholino gene knockdown studies, new insights into early mast cell transcriptional regulation and ontogeny have been exposed in vivo. Transgenic strategies have permitted the modeling of human mast cell diseases, like systemic mastocytosis in zebrafi sh, which can subsequently be exploited for high-throughput chemical screens to identify potential therapies in these conditions. Mast cell functional assays have been adapted to zebrafi sh providing the opportunity to utilize this model for interrogating the cellular players in innate and adaptive immunity and as a live animal readout for drug responses in allergic and infl ammatory reactions. These techniques are detailed in the following chapter.