Synapse formation between central neurons requires postsynaptic expressionof the MEN1 tumor suppressor gene

Synapse formation is a crucial step in the development of neuronal circuits and requires precise coordination of presynaptic and postsynaptic activiti es. However, molecular mechanisms that control the formation of functionall y mature synaptic contacts, in particular between central neurons, remain p oorly understood. To identify genes that are involved in the formation of c entral synapses, we made use of molluscan neurons that in culture form syna ptic contacts between their somata (soma-soma synapses) in the absence of n eurite outgrowth. Using single-cell mRNA differential display, we have iden tified a molluscan homolog of the multiple endocrine neoplasia type 1 (MEN1 ) tumor suppressor gene encoding the transcription factor menin as a gene t hat is upregulated during synapse formation. In vitro antisense knock-down of MEN1 mRNA blocks the formation of mature synapses between different type s of identified central neurons. Moreover, immunocytochemistry and cell-spe cific knock-down of MEN1 mRNA show that postsynaptic but not presynaptic ex pression is required for synapses to form. Together, our data demonstrate t hat menin is a synaptogenic factor that is critically involved in a general postsynaptic mechanism of synapse formation between central neurons.