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The Role of GSK3β in Regulating Neuronal Differentiation inXenopus laevis

https://doi.org/10.1006/mcne.1998.0713Get rights and content

Abstract

The serine threonine protein kinase encoded by theshaggylocus has been implicated in neurogenesis inDrosophila.In vertebrates, the shaggy homolog,GSK3β, is involved in early pattern formation, specifically in setting up the dorsal ventral axis. In the present study we have cloned theXenopushomolog of the shaggy kinase and show (1) that GSK3β is expressed in the right time and place to play a role in primary neurogenesis inXenopus;(2) that overexpression of wild-type GSK3β leads to a decrease in the number of primary neurons; (3) that inhibition of endogenous GSK3β activity with overexpression of a dominant negative GSK3β construct leads to an increase in the number of primary neurons; and (4) that GSK3β 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 GSK3β inhibits the function of NeuroD and therefore prevents neuronal differentiation at a relatively late stage in the developmental pathway.

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    1

    To whom correspondence and reprint requests should be addressed at present address: Cell Press, 1050 Massachusetts Ave., MA 02138. Fax: (617) 661-7061. E-mail:[email protected].

    2

    Department of Anatomy, University of Cambridge, Cambridge, CB23DY, UK.

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