Wnts of Change

Dr. Budnik was a graduate student in Kalpana White’s lab from 1984 to 1988. Here she studied various modes of neurotransmission in the fruit fly brain.

Activity-dependent modifications in synaptic structure play a key role in synaptic plasticity and the development of neuronal circuits. However, the signaling mechanisms underlying this process are still poorly understood. Budnik demonstrated that glutamatergic Drosophila larval neuromuscular junctions (NMJs) undergo rapid and dynamic changes in synaptic structure and function in response to patterned stimulation. These changes, which depend on transcription and translation, include the formation of highly motile presynaptic filopodia-like structures, the elaboration of undifferentiated presynaptic varicosities, and potentiation of spontaneous release frequency. Experiments indicate that a bidirectional Wnt/Wg (Wingless) transduction pathway underlies these changes. Evoked activity induces Wnt1/Wg release from synaptic boutons, which stimulates both a postsynaptic DFz2 nuclear import pathway, as well as a presynaptic pathway involving GSK-3ß/Shaggy. The findings suggest that bidirectional Wg signaling operates downstream of synaptic activity to induce modifications in synaptic structure and function. Budnik proposes that activation of the postsynaptic Wg pathway is required for the assembly of the postsynaptic apparatus, while activation of the presynaptic Wg pathway regulates cytoskeletal dynamics. This mechanism might operate directly or through the activation of known plasticity pathways such as PKA and CREB.