Synaptic differentiation during development is a multi-step process, which requires reciprocal communication between pre- and postsynaptic cells. Cell surface interactions can induce the assembly of synaptic specializations but maintenance and growth of synapses depend on transcriptional regulation. Transcriptional responses associated with synaptic differentiation are observed in central and peripheral neurons and depend on retrograde signals coming from the target region. Although the identity of most of the retrograde signaling pathways remains to be identified, the TGFbeta family of growth factors have emerged as one crucial signal at the neuromuscular junction. Here, we discuss evidence for transcriptional control during synaptic differentiation and the signaling pathways mediating retrograde TGFbeta signaling.