The role of Frizzled receptors in the assembly of central synapses.

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The formation of a functional brain requires the assembly of appropriate nerve connections. During development, nerve cells (neurons) extend long processes called axons in search for their target to subsequently form connections (synapses). Synapses contain two main components, the presynaptic terminal that releases neurotransmitter and the postsynaptic terminal (in the target) that is receptive to neurotransmitters so that an electrical impulse is transmitted from one terminal (presynaptic) to another neurons (the postsynaptic terminal). After reaching their targets, axons receive signals that stimulate the assembly of synapses. However, the mechanisms by which nerve cells interpret these signals to initiate the assembly of the machinery involved in neurotransmitter release remains poorly understood. Our laboratory has been studying the function of Wnts, molecules released by synaptic targets, in the formation of nerve connections in the mammalian brain. Wnts induce the recruitment of key molecules to specific areas of the axon resulting in the formation of functional synapses. However, the mechanisms that control where synapses are formed remain poorly understood. This proposal addresses the mechanisms by which neurons respond to signals to assembly synapses at the right place. Using neuronal cell cultures and mutant mice, we plan to examine how extracellular signals called Wnts are interpreted by receptive cells to stimulate the formation and maintenance of synapses at specific locations. New studies suggest that neuronal cell loss observed in neurodegenerative diseases such as Parkinson and Alzheimer?s are trigged by the loss of synapses. Therefore, understanding the mechanisms that regulate how synapse are formed and maintained is crucial for the development of therapeutic strategies for the treatment and/or prevention of neuronal degeneration.