A chemical genetic approach reveals distinct EphB signaling mechanisms during brain development.

The EphB family of receptor tyrosine kinases can signal bidirectionally and functions in a kinase-dependent and kinase-independent manner. To determine the importance of the kinase activity of EphBs for axonal guidance and synaptogenesis, the authors used a chemical genetic method and generated knock-in mice that allow the kinase activity of EphBs to be inhibited without altering kinase-independent functions of EphBs. They find that specific inhibition of EphB kinase activity had no effect on synaptogenesis, but impaired axonal guidance, thereby implicating the kinase function of EphB in one neuronal process, but not other processes that are nevertheless dependent on EphBs.