FUNCTION OF THE CHEMOKINE RECEPTOR CXCR4 IN HEMATOPOIESIS AND IN CEREBELLAR DEVELOPMENT

Chemokines and their receptors are important in cell migration during inflammation(1), in the establishment of functional lymphoid microenvi ronments(2), and in organogenesis(3). The chemokine receptor CXCR4 is broadly expressed in cells of both the immune and the central nervous systems(4,5) and can mediate migration of resting leukocytes and haema topoietic progenitors in response to its ligand, SDF-1 (refs 6-9). CXC R4 is also a major receptor for strains of human immunodeficiency viru s-1 (HIV-1) that arise during progression to immunodeficiency and AIDS dementia(10). Here we show that mice lacking CXCR4 exhibit haematopoi etic and cardiac defects identical to those of SDF-1-deficient mice(3) , indicating that CXCR4 may be the only receptor for SDF-1. Furthermor e, fetal cerebellar development in mutant animals is markedly differen t from that in wild-type animals, with many proliferating granule cell s invading the cerebellar anlage. This is, to our knowledge, the first demonstration df the involvement of a G-protein-coupled chemokine rec eptor in neuronal cell migration and patterning in the central nervous system. These results may be important for designing strategies to bl ock HIV entry into cells and for understanding mechanisms of pathogene sis in AIDS dementia.