Wdr1 deficiency causes cytoskeletal defects in neutrophils. (A) Neutrophil chemotaxis toward MIP-2 in 3-micron transwells, demonstrating defective migration of Wdr1^rd/rd neutrophils. (B) Basal and MIP-2–stimulated actin polymerization, showing elevated resting filamentous actin levels and impaired actin depolymerization rates in Wdr1^rd/rd neutrophils. Data shown represent the means plus or minus a standard deviation; n equals 6 mice per genotype. (C) Fluorescence microscopy showing the cellular distribution of filamentous actin in neutrophils. In wild-type cells, filamentous actin is distributed throughout the cytosol and is more concentrated at the cell cortex. In Wdr1^rd/rd neutrophils, the formation of filamentous actin is enhanced with no obvious cortical actin. (D) Cellular localization of cofilin in neutrophils. In wild-type cells, cofilin is localized to the nucleus and to the periphery (white arrows). In contrast, in Wdr1^rd/rd neutrophils cofilin is delocalized from the cell cortex and becomes diffused throughout the cytosol. (E) Transmission electron microscopy of peripheral blood neutrophils. No gross morphologic changes were seen in Wdr1^rd/rd neutrophils. Scale bar indicates 1 μm.