The bone marrow produces millions of platelets every hour. Lin Zhang et al. now find that platelet production in mice requires signaling by the lipid mediator sphingosine 1-phosphate (J. Exp. Med. 209, 2165–2181, 2012).

In the last steps of platelet production, megakaryocytes extend pseudopods, termed proplatelets, into the lumen of bone marrow sinusoids. Platelets are then shed from the tips of the proplatelets into the blood. The researchers showed that both of these steps are controlled by sphingosine 1-phosphate signaling through the sphingosine 1-phosphate receptor S1pr1 on megakaryocytes. Proplatelet extension requires a transendothelial gradient of sphingosine 1-phosphate, and platelet shedding occurs in response to the high concentrations of sphingosine 1-phosphate in the blood.

A drug that acts on sphingosine 1-phosphate receptors, fingolimod, is approved for the treatment of multiple sclerosis. Pointing to the potential clinical utility of targeting sphingosine 1-phosphate signaling for treating thrombocytopenia, the authors showed that treating mice with fingolimod accelerated platelet shedding and resulted in increased platelet counts.