This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project focuses on the identification and characterization of proteins capable of inducing the formation of neuron-neuron synaptic contacts. Synapse formation is a highly orchestrated process that involves cell-cell interactions carried out by distinct groups of molecules which participate in target recognition, contact stabilization, and functional coupling between pre and postsynaptic compartments. Our central hypothesis is that the expression of membrane tethered or secreted ligands by the presumptive postsynaptic neuron, is required to induce the differentiation of the presynaptic terminal and the stabilization of the synaptic contact, which will lead the functional coupling between synaptic compartments. Using a genome-wide search of genes that become activated during synapse development in intact neural tissue we identified a group of gene transcripts encoding membrane-bound and secreted proteins that are specifically expressed during the initial phase of synapse formation. The current proposal is aimed at examining whether these proteins are sufficient to induce synapse formation. The proteins with synaptogenic activity will be further study in the future to determine whether they are necessary for inducing synapse formation in vivo, and to analyze the molecular mechanisms responsible for their synaptogenic activity. As synapses are the centerpiece of neuronal communication and become affected in a variety of mental and neurological disorders, the discovery of the molecules and the understanding of the mechanisms that participate in the establishment of synaptic connections will contribute to our understanding of both, the normal formation and function of neuronal circuits, and the causes of mental and neurological illnesses.
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