Chemokines beyond inflammation

The CXCR4 chemokine receptor is expressed throughout the body, and is a co-receptor⁵ for cellular entry by T-cell-tropic but not macrophage-tropic strains of HIV-1. Its ligand is the stromal derived factor SDF-1 (ref. 6), which is known to be important in embryonic development⁷. Mice that lack the SDF-1 gene die in utero, with severe defects in the ventricular septum of the heart. They also have fewer B-lymphocyte progenitors in the liver and bone marrow, suggesting defects in the formation of red and white blood cells. An obvious question is whether deletion of the CXCR4 receptor would produce a similar profile of deficiencies, and this is now addressed by Tachibana et al. and Zou et al. Although they find that CXCR4-deficient mice have a similar phenotype to the SDF-1 knockouts, the results also hold some surprises.

The two groups show that when both copies of the CXCR4 gene are knocked out, around half the mice die in utero by the 18th day of embryological development (E18.5), the remainder dying within one hour of birth. The similarity of this phenotype to that of the SDF-1-knockout mice confirms that CXCR4 and SDF-1 are a specific receptor-ligand pair that act in cardiac and blood-cell development. But the real surprise to come from the knockout mice is that CXCR4 is involved in the embryological development of neuronal networks in the central nervous system (CNS) and in the development of blood vessels in the gastrointestinal tract.