Importantly, WASp is required for the formation of podosomes and tyrosine phosphorylation of WASp has been shown to regulate actin dynamics inside podosomes. Therefore it is possible that WASp may be required to stabilize the chemotactic protrusions by promoting cell-substrate interactions. While lack of adhesion may account for the increased retraction rate observed in the absence of WASp, it does not account for the observed delay in the onset of protrusions in the absence of WASp or its phosphorylation suggesting that WASp may play multiple roles in chemotactic protrusions. In conclusion, our data show that WASp is required for the first wave of actin assembly in response to CSF-1 that leads to the establishment of persistence of chemotactic protrusions of macrophages. We also show that tyrosine phosphorylation state of WASp plays a role in the initiation of chemotactic protrusion. A key question remains, which is how WASp activity is regulated and maintained in a temporally and spatially controlled manner for successful protrusion persistence and chemotaxis to take place. While further studies will be required to elucidate the molecular mechanism that regulate WASp activity during macrophage migration, the data presented herein highlight the critical role of WASp in the establishment of persistence of protrusion in macrophage chemotaxis. breast cancer; however it is associated with many unwanted side effects. One such effect is cognitive impairment, which can encompass lack of concentration, problems with memory formation and general confusion and has been reported to last for up to several years after completion of chemotherapy treatment. With the increasing survival of cancer sufferers, it is becoming important to understand the causes of chemotherapy induced cognitive impairment and to find ways to prevent it and improve patient quality of life. The antimetabolite, 5-fluorouracil, is commonly used in combination with other agents to treat cancer and has been associated with cognitive impairment in patients. Its ability to cross the blood-brain barrier by passive diffusion enables it to affect the brain when given systemically. A small number of studies, performed in rodents, have previously examined the effects of 5-FU, with the majority finding that the drug impaired cognition and suppressed hippocampal cell proliferation. Consequently, the cytotoxic effect of chemotherapy on the proliferation of neural stem and precursor cells required for adult hippocampal neurogenesis has been considered as a possible mechanism for chemotherapy-induced cognitive impairment. The subgranular zone of the dentate gyrus is one of a limited number of regions where neurogenesis persists throughout adulthood. Memory formation and spatial memory are both functions of the hippocampus and the proliferation and integration of the neuronal precursors into existing circuits is thought to play a functional role in this Axitinib process. Fluoxetine, a selective serotonin reuptake inhibitor antidepressant, has been shown to increase cell proliferation in the hippocampus in both rodents and humans and improve memory in patients with impaired cognition. Furthermore, recent rodent investigations in our group showed that fluoxetine can reverse the impaired spatial memory and reduced proliferation of hippocampal cells caused by treatment with 5-FU and methotrexate chemotherapy.