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Diffusible signaling at the neuromuscular junction

Researcher
Franklin Carrero-Martínez, Ph.D

Abstract

Targeting cytosolic molecules to membrane is an extremely effective means to enhance (“activate”) their functions. Previously, due to limited access in embryos, the mechanisms that initiate a new synapse have rarely been analyzed in vivo. Previously, we started dissecting synaptogenesis using uniquely identified synapses in Drosophila and proposed a model that integrates both cellular and molecular components. Using GFP- labeling together with live imaging, we showed that every neuromuscular synapse in live, intact embryos is preceded by a transient stabilization/clustering of presynaptic and postsynaptic filopodia from matched partners upon their initial contact.
One of the first postsynaptic cytosolic molecules that enter this newly-created filopodial cytoplasm is Dlg, a member of PSD-95 family of scaffolding proteins. Although not essential for the formation of the filopodial cluster, Dlg is required to maintain the contact between the axon and target muscle while a nascent synapse progressively attains its functionality.
Individual myopodia grows and adjusts its directionality in order to contact presynaptic filopodia. Filopodial clustering results from the progressive stabilization of individual myopodia after initial contact with presynaptic filopodia. Filopodial interactions between nonpartner cells, though extensive and essential for proper axon guidance, do not lead to such a filopodial behavior. Over-expression of a dominant-negative Ezrin in targets eliminates this filopodial clustering and, disrupts normal synaptogenesis. Taken together, these observations suggest a two-way communication between partner cells prior to their initial physical contact that results in myopodial cluster formation. Here, we propose to study the role diffusible signaling molecules in myopodial clustering formation as a prerequisite for successful




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