What signals control synaptogenesis? We have previously demonstrated that astrocytes secrete a factor that increases the number of synapses on purified CNS neurons 7-fold (Science 2001 Jan 26:657-61). We have now identified two proteins that may play a crucial role in this process. First, we have identified a secreted molecule synthesized by astrocytes that is sufficient to induce structural synaptogenesis in vitro as assessed by immunocytochemistry and electron microscopy. This factor increases synapse number in a dose-dependent manner. Immunodepletion of this factor significantly reduces the synapse-promoting activity of ACM, indicating that this protein is necessary for the synapse-promoting activity and that extrinsic, astrocyte-derived proteins are able to regulate synapse number on neurons. We are currently identifying the receptor for this protein. Surprisingly, this protein is not sufficient to induce electrically active synapses (Ullian et. al., SFN 2003 abstract). Second, we have found an additio...