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

Development. 2009 Apr;136(8):1273-82. doi: 10.1242/dev.031377.

Abstract

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-3beta (Gsk-3beta). Conversely, ectopic expression of activated Gsk-3beta 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-3beta is a key sensor involved in neural circuit integrity, maintaining axon stability through neural activity and the Wnt pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Animals, Genetically Modified
  • Down-Regulation
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Gene Expression Regulation, Developmental
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Mutation / genetics
  • Neuroglia / metabolism
  • Olfactory Bulb / growth & development*
  • Olfactory Bulb / metabolism*
  • Receptors, Odorant / deficiency
  • Receptors, Odorant / genetics
  • Receptors, Odorant / metabolism
  • Sensory Receptor Cells / metabolism*
  • Signal Transduction*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism

Substances

  • Drosophila Proteins
  • Orco protein, Drosophila
  • Receptors, Odorant
  • Wnt Proteins
  • Wnt1 Protein
  • wg protein, Drosophila
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3