© 2003 Nature Publishing Group 444 | JUNE 2003 | VOLUME 4 www.nature.com/reviews/neuro REVIEWS Chemokines are a family of small proteins, originally shown to play a pivotal part in the control of leukocyte trafficking 1 . Although this is still the function that is most studied, chemokines have now been shown to be of key importance in the overall organization of the entire haematopoietic/lymphopoietic system, including the regulation of stem cell maturation, the formation of secondary lymphoid tissues and angiogenesis 2–5 . Moreover, because chemokines and their receptors are also intimately involved in the orchestration of inflam- matory responses and in the pathogenesis of AIDS 6 , they are considered to be important potential therapeutic targets in these diseases 7 . Based on recent findings that chemokines and their receptors are involved in control- ling organogenesis, as well as the maturation and migration of different types of stem cells 8–12 , it is now becoming clear that chemokine mediated signalling might have a wider influence than originally anticipated. So, apart from the haematopoietic/lymphopoietic system, chemokines probably have important roles in the development and homeostasis of all tissues. What then, if anything, do chemokines have to do with the nervous system? It is well known that chemokines and their receptors are important in neuroinflammatory disease 13 . In keeping with their traditionally defined roles as organizers of the immune system, chemokines have been shown to be of central importance in guiding leukocytes to sites of inflamma- tion in the brain. Recent work has established that all of the major cell types in the brain — including microglia, glia and neurons — express various chemokine receptors, making them potential targets for the actions of chemokines. Furthermore, it is known that these differ- ent cell types can synthesize chemokines, indicating that in the brain, there is an independent chemokine effector/receptor system. So, it seems that chemokines might have a more complex role in the nervous system, extending beyond their known role as local mediators of immune responses. Although these observations are intriguing, they also raise interesting questions. For instance, do the effects of chemokines in the brain merely recapitulate their well- established effects on leukocytes, or is something else afoot? Furthermore, why do mature neurons that are firmly integrated into neuronal circuits express chemokine receptors, especially as it is hard to imagine a chemotactic function in this case? A series of papers published over the last few years have started to provide CHEMOKINE RECEPTORS: SIGNPOSTS TO BRAIN DEVELOPMENT AND DISEASE Phuong B. Tran and Richard J. Miller During the development of the nervous system, populations of progenitor cells that eventually become neurons and glia face the complex task of finding their way from their place of birth to their final destinations. What are the molecular processes that provide the information for guiding progenitor cells along their way? In this article, we discuss recent information indicating that chemokines and their receptors are of great importance in directing the proliferation and migration of immature neurons, glia and their precursors. Furthermore, chemokine receptor function in the nervous system continues to be important throughout adult life, and chemokines participate in various brain disorders, including AIDS dementia, neuroinflammatory disease and neuroplasia, making them important potential therapeutic targets in these cases. Department of Molecular Pharmacology & Biological Chemistry, Northwestern University, Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, Illinois 60611, USA. Correspondence to R.J.M. e-mail: r-miller10@northwestern.edu doi:10.1038/nrn1116