These authors contributed equally to this study.
Transcriptomic profiles of Wnt3a and insulin in primary cultured rat cortical neurones
Article first published online: 1 JUL 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 118, Issue 4, pages 512–520, August 2011
How to Cite
Hooper, C., Killick, R., Fernandes, C., Sugden, D. and Lovestone, S. (2011), Transcriptomic profiles of Wnt3a and insulin in primary cultured rat cortical neurones. Journal of Neurochemistry, 118: 512–520. doi: 10.1111/j.1471-4159.2011.07349.x
- Issue published online: 14 JUL 2011
- Article first published online: 1 JUL 2011
- Accepted manuscript online: 14 JUN 2011 03:18AM EST
- Received January 31, 2011; revised manuscript received May 27, 2011; accepted May 30, 2011.
Vol. 123, Issue 1, 202, Article first published online: 16 AUG 2012
- glycogen synthase kinase;
- target genes;
J. Neurochem. (2011) 118, 512–520.
Glycogen synthase kinase 3 (GSK3) is a widely expressed, constitutively active, serine/threonine kinase that is negatively regulated by both Wnt and insulin via two independent signalling pathways. GSK3 is an important mediator in many physiological processes including glycogen metabolism, apoptosis and gene transcription. In addition, GSK3 is implicated in diseases such as Alzheimer’s, schizophrenia and cancer, where it exhibits deregulated activity. In this study, we sought to determine the neuronal genes regulated by both Wnt and insulin in an in vitro cell culture model to further elucidate the signalling roles GSK3 plays in the CNS. Affymetrix Rat Genome 230 2.0 whole genome microarrays were used to explore the expression profiles of rat primary cortical neurones treated with recombinant Wnt3a (10 nM) or insulin (50 nM) for 2 h. Following a conservative correction (Bonferroni) for multiple testing, seven genes were identified to be differentially expressed from controls; four of these genes were regulated by insulin and three genes were regulated by both insulin and Wnt3a. The data were also analysed using a false discovery rate cut off, which is a less stringent correction for multiple testing. This approach yielded 105 genes that were differentially regulated from controls; 72 of the gene changes were attributable to insulin treatment, 11 were because of Wnt3a treatment and 22 genes were altered by both insulin and Wnt3a. These data demonstrate that the Wnt and insulin pathways exhibit both divergent and overlapping signalling activities in neuronal cells. The overlapping transcriptional response was not attributable to Wnt3a activating Akt. These findings have ramifications for neurodevelopment and neurological diseases, in which the Wnt and insulin signalling pathways are implicated.