Fig. P1.

Astrocyte-secreted proteins hevin and SPARC control excitatory synaptogenesis in vitro and in vivo. Hevin induces the formation of synapses. SPARC is not synaptogenic, but specifically inhibits the synaptogenic function of hevin. Furthermore, we found that lack of hevin leads to defects in the recruitment of pre- and postsynaptic specializations at the RGC synapses in vitro and in vivo. These results identify hevin as a positive and SPARC as a negative regulator of synaptic development, and signify that, through regulation of relative levels of hevin and SPARC, astrocytes control the formation, maturation, and plasticity of synapses in the CNS.