The role of GSK3beta 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, GSK3beta, 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 GSK3beta is expressed in the right time and place to play a role in primary neurogenesis in Xenopus; (2) that overexpression of wild-type GSK3beta leads to a decrease in the number of primary neurons; (3) that inhibition of endogenous GSK3beta activity with overexpression of a dominant negative GSK3beta construct leads to an increase in the number of primary neurons; and (4) that GSK3beta inhibits the ability of neurogenin and NeuroD to produce ectopic tubulin expression, but does not inhibit the ability of neurogenin to produce ectopic NeuroD. On the basis of these data we propose that GSK3beta inhibits the function of NeuroD and therefore prevents neuronal differentiation at a relatively late stage in the developmental pathway.