The actin regulatory factor Wiskott–Aldrich syndrome protein (WASp) coordinates the dynamic polymerisation of the actin cytoskeleton through the Arp2/3 complex and acts downstream of Cdc42. WASp has been linked to immunodeficiency disorders such as WAS, which exhibits truncated or abolished protein expression, and also to neurodegenerative disorders such as X-linked neutropenia (XLN), which results from constitutively active WASp mutants. The functions of WASp have been studied extensively in vitro. For instance, innate immune cells deficient in WASp were shown to display abnormal chemotaxis, motility and phagocytosis, but in vivo experiments proved challenging. Paul Martin and co-workers now (p. 4077) first characterise the effects the lack of WASp has in zebrafish larvae by using live imaging in vivo before dissecting the functions of specific human WASp mutants expressed in leukocytes of WASp-null zebrafish. They confirm that deletion of zebrafish WASp mirrors the phenotype of WAS in humans and show that expression of different human WASp mutants, including phosphorylation mutants and an XLN-associated form, in these larvae also reflects the respective human phenotypes with regard to their ability to generate neutrophils, their chemotactic response to wounding and the phagocytic capacity of macrophages. Taken together, these results establish a model to investigate WASp function in vivo and demonstrate the potential of using live imaging of zebrafish larvae in order to observe the behaviour of immune cells.
- © 2013. Published by The Company of Biologists Ltd