The role of GSK3β in regulating neuronal differentiation in Xenopus laevis

The serine threonine protein kinase encoded by the shaggy locus has been implicated in neurogenesis in Drosophila. In vertebrates, the shaggy homolog, GSK3 beta, is involved in early pattern formation, specifically in setting up the dorsal ventral axis. In the present study we have cloned the Xenopus homolog of the shaggy kinase and show (1) that GSK3 beta is expressed in the right time and place to play a role in primary neurogenesis in Xenopus; (2) that overexpression of wild-type GSK3 beta leads to a decrease in the number of primary neurons; (3) that inhibition of endogenous GSK3 beta activity with overexpression of a dominant negative GSK3 beta construct leads to an increase in the number of primary neurons; and (4) that GSK3 beta inhibits the ability of neurogenin and NeuroD to produce ectopic tubulin expression, but does not inhibit the ability of neurogenin to produce ectopic Neuron. On the basis of these data we propose that GSK3 beta inhibits the function of Neuron and therefore prevents neuronal differentiation at a relatively late stage in the developmental pathway.