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First published online March 20, 2009
doi: 10.1242/10.1242/dev.031377

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Neuronal activity and Wnt signaling act through Gsk3-β to regulate axonal integrity in mature Drosophila olfactory sensory neurons

¹ National Centre for Biological Sciences, TIFR, GKVK Campus, Bangalore-65, India.
² Smurfit Institute of Genetics and TCIN, Lloyd Building, Trinity College Dublin, Dublin-2, Ireland.
³ Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA.
⁴ Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai-5, India.

^* Authors for correspondence (e-mails: vijay{at}ncbs.res.in; veronica{at}ncbs.res.in)

Accepted 10 February 2009

The roles played by signaling pathways and neural activity during the development of circuits have been studied in several different contexts. However, the mechanisms involved in maintaining neuronal integrity once circuits are established are less well understood, despite their potential relevance to neurodegeneration. We demonstrate that maintenance of adult Drosophila olfactory sensory neurons requires cell-autonomous neuronal activity. When activity is silenced, development occurs normally, but neurons degenerate in adulthood. These detrimental effects can be compensated by downregulating Glycogen synthase kinase-3β (Gsk-3β). Conversely, ectopic expression of activated Gsk-3β or downregulation of Wnt effectors also affect neuron stability, demonstrating a role for Wnt signaling in neuroprotection. This is supported by our observation that activated adult neurons are capable of increased Wingless release, and its targeted expression can protect neurons against degeneration. The role of Wnt signaling in this process is non-transcriptional, and may act on cellular mechanisms that regulate axonal or synaptic stability. Together, we provide evidence that Gsk-3β is a key sensor involved in neural circuit integrity, maintaining axon stability through neural activity and the Wnt pathway.

Key words: Drosophila, Olfactory system, Neuronal activity, Gsk-3β (Shaggy), Wingless

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